Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

Unveiling behaviors of 8:2 fluorotelomer sulfonic acid (8:2 FTSA) in Arabidopsis thaliana: Bioaccumulation, biotransformation and molecular mechanisms of phytotoxicity.

8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.

Metabolome and transcriptome analyses identify the characteristics and expression of related saponins of the three genealogical plants of bead ginseng.

Objective: The classification and clinical usage of the different species of bead ginseng are often confused. Therefore, we conducted an integrated metabolomics and transcriptome analysis of three main species of Panax, including Panax japonicas, Panax pseudoginseng, and Panax pseudo-ginseng var. elegantior. Methods: A broad metabolome and transcriptome analysis for three origins of bead ginseng plants was performed using UPLC-ESI-MS/MS, RNA sequencing and annotation, and bioinformatic analysis of transcriptome data. Results: The levels of 830 metabolites were determined. A total of 291 differentially accumulated metabolites (DAMs) between Panax pseudo-ginseng var. elegantior and Panax japonicas (Group A), with 73 upregulated and 218 downregulated. A total of 331 DAMs (110 upregulated and 221 downregulated) were found between Panax pseudoginseng and Panax japonicas (group B). There were 160 DAMs (102 up-regulated and 58 down-regulated) between Panax pseudoginseng and Panax pseudo-ginseng var. elegantior (group C). In addition, RNA sequencing was performed in the above three ways. A total of 16,074 differential expression genes (DEGs) were detected between Group A, in which 7,723 genes were upregulated and 8,351 genes were downregulated by RNA sequencing. Similarly, 15,705 genes were differentially expressed between group B, in which 7,436 genes were upregulated and 8,269 genes were downregulated. However, only 1,294 genes were differentially expressed between group C, in which 531 genes were upregulated and 763 genes were downregulated. We performed differential gene analysis on three groups of samples according to the Venn diagram and found that 181 differential genes were present. A total of 3,698 and 2,834 unique genes were in groups A and B, while 130 unique genes were in group C. Conclusions: This study provides metabolome and transcriptome information for three bead ginseng plants. The analysis of the metabolite content showed differences in the attributes of the three bead ginseng, contained mainly flavonoids, phenolic acids as well as terpenes.

Programmable and printable formaldehyde dehydrogenase as an excellent catalyst for biodegradation of formaldehyde.

As an environmental pollutant, formaldehyde can cause serious harm to the human body. Among many degradation methods, formaldehyde dehydrogenase from Pseudomonas putida (PFDH) exhibits broad potential because of its strong catalytic specificity and high degradation efficiency. However, the real application of PFDH in industry is limited by its instability and difficulties in recycling. In this work, the suitable printing conditions for immobilizing PFDH by three-dimensional (3D) printing technology were studied: the concentration of sodium alginate (SA) was 1.635 wt%, the concentration of CaCl2 was 7.4 wt%, the crosslinking time with CaCl2 was 8 min, and the temperature of the reaction was 31.5°C. 3D-printed PFDH/calcium alginate (CA) microspheres have 210% relative enzyme activity after seven repeated uses. Dried PFDH/CA particles were characterized by scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), EDS elemental mapping, and thermogravimetric analysis (TGA) which proved that the enzyme was immobilized by the material. In addition, the recycling ability of 3D printing to immobilize different objects was explored and different shapes were designed by computer-aided design (CAD). In conclusion, 3D printing technology was applied to immobilize PFDH in this work, which provides a new idea to biodegrade formaldehyde in a green way.

Degradation of 8:2 fluorotelomer carboxylic acid (8:2 FTCA) by plants and their co-existing microorganisms.

8:2 fluorotelomer carboxylic acid (8:2 FTCA), an important precursor of perfluorocarboxylic acids (PFCAs), is widely detected in environment and biotas. Hydroponic exposures were conducted to investigate the accumulation and metabolism of 8:2 FTCA in wheat (Triticum aestivum L.) and pumpkin (Cucurbita maxima L.). Endophytic and rhizospheric microorganisms co-existing with the plants were isolated to investigate their contributions to degrade 8:2 FTCA. Wheat and pumpkin roots could take up 8:2 FTCA efficiently with the root concentration factor (RCF) as 5.78 and 8.93, respectively. 8:2 FTCA could be biotransformed to 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA), 7:3 fluorotelomer carboxylic acid (7:3 FTCA), and seven PFCAs with 2-8 carbon chain length in plant roots and shoots. Cytochromes P450 (CYP450) and glutathione-S-transferase (GST) activities in plants were significantly increased, while flavin-dependent monooxygenases (FMOs) activities were not changed, suggesting that CYP 450 and GST were involved in the transformation of 8:2 FTCA in plant tissues. Twelve 8:2 FTCA-degrading endophytic (8 strains) and rhizospheric (4 strains) bacterial strains were isolated from root interior, shoot interior and rhizosphere of plants, respectively. These bacteria were identified as Klebsiella sp. based on the morphology and 16S rDNA sequence, and they could biodegrade 8:2 FTCA to intermediates and stable PFCAs.

Real-world application of a fast stool DNA test for colorectal cancer screening in primary screening positive population.

BACKGROUND: Stool DNA test has been emerged as an effective noninvasive method for colorectal cancer (CRC) screening, but the real-world performance of stool DNA test in Chinese population has rarely been reported. METHODS: A total of 36,527 subjects were recruited in Haining City from January 2021 to December 2021. Participants underwent primary screening by taking both two-samples fecal immunochemical tests (FITs) and high-risk factor questionnaire (HRFQ), and those who tested either positive by FITs or evaluated to be high risk by HRFQ were recommended to undertake subsequent stool DNA test and colonoscopy. RESULTS: Of 36,527 participants, 34,778 (95%) completed both HRFQ and FITs, 9947 (29%) showed positive results during primary screening, and the colonoscopy compliance rate was 49%. Of primary screening positives, 8733 (88%) completed stool sample collections, and colonoscopy results from 4293 eligible participants were used for analyzing the performance of stool DNA test. The sensitivities for detecting CRC and advanced adenomas (AA) were 100% (95% CI: 60-100%) and 40% (95% CI: 34-46%), and the area under curve (AUC) was 0.961 (95% CI:0.954-0.967) and 0.625 (95% CI: 0.609-0.641), respectively. The specificity of stool DNA test was 84% (95% CI: 82-85%). The false-positive rate for stool DNA test is about 10% less than that of primary screening. CONCLUSION: Stool DNA test is a cost-effective and promising alternative strategy for CRC screening in China.

A conceptual framework of cognitive-affective theory of mind: towards a precision identification of mental disorders.

To explore the minds of others, which is traditionally referred to as Theory of Mind (ToM), is perhaps the most fundamental ability of humans as social beings. Impairments in ToM could lead to difficulties or even deficits in social interaction. The present study focuses on two core components of ToM, the ability to infer others' beliefs and the ability to infer others' emotions, which we refer to as cognitive and affective ToM respectively. Charting both typical and atypical trajectories underlying the cognitive-affective ToM promises to shed light on the precision identification of mental disorders, such as depressive disorders (DD) and autism spectrum disorder (ASD). However, most prior studies failed to capture the underlying processes involved in the cognitive-affective ToM in a fine-grained manner. To address this problem, we propose an innovative conceptual framework, referred to as visual theory of mind (V-ToM), by constructing visual scenes with emotional and cognitive meanings and by depicting explicitly a four-stage process of how humans make inferences about the beliefs and emotions of others. Through recording individuals' eye movements while looking at the visual scenes, our model enables us to accurately measure each stage involved in the computation of cognitive-affective ToM, thereby allowing us to infer about potential difficulties that might occur in each stage. Our model is based on a large sample size (n > 700) and a novel audio-visual paradigm using visual scenes containing cognitive-emotional meanings. Here we report the obtained differential features among healthy controls, DD and ASD individuals that overcome the subjectivity of conventional questionnaire-based assessment, and therefore could serve as valuable references for mental health applications based on AI-aided digital medicine.

Construction of self-learning classroom history teaching mode based on human-computer interaction emotion recognition.

Due to the continuous epidemic in recent years, the traditional teaching mode of history classroom has been gradually replaced by the teaching mode of self-learning classroom. The teaching mode of autonomous learning classroom has become a popular teaching mode in recent years. However, in the autonomous learning classroom under the current history teaching mode, the lecturer cannot always pay attention to the various states of the students. It is also difficult to understand and receive the information the teacher wants to convey in real time. For this reason, human-computer interaction emotion recognition technology has been proposed and developed. In order to construct and realize the teaching mode of self-learning classroom history, this paper studies the emotion recognition technology of human-computer interaction. The research results show that the introduction of human-computer interaction emotion recognition technology into the construction of autonomous learning classroom teaching mode can fully understand students' emotional behavior. It improves the accuracy of students' emotion recognition by 2.67%, enables students to maintain a good learning motivation, and make reasonable plans and arrangements for the historical time and progress of learning. At the same time, it enhances the history teaching intensity and autonomous learning ability, and improves the original single learning mode. By establishing a new teaching-teacher-student relationship, it creates a good and active autonomous classroom atmosphere.

Engineering and screening of novel ß-1,3-xylanases with desired hydrolysate type by optimized ancestor sequence reconstruction and data mining.

Engineering of hydrolases to shift their hydrolysate types has not been attempted so far, though computer-assisted enzyme design has been successful. A novel integrative strategy for engineering and screening the ß-1,3-xylanase with desired hydrolysate types was proposed, with the purpose to solve problems that the separation and preparation of ß-1,3-xylo-oligosaccharides was in high cost yet in low yield as monosaccharides existed in the hydrolysates. By classifying the hydrolysate types and coding them into numerical values, two robust mathematical models with five selected attributes from molecular docking were established based on LogitBoost and partial least squares regression with overall accuracy of 83.3% and 100%, respectively. Then, they were adopted for efficient screening the potential mutagenesis library of ß-1,3-xylanases that only product oligosaccharides. The virtually designed AncXyl10 was selected and experimentally verified to produce only ß-1,3-xylobiose (60.38%) and ß-1,3-xylotriose (39.62%), which facilitated the preparation of oligosaccharides with high purity. The underlying mechanism of AncXyl10 may associated with the gap processing and ancestral amino acid substitution in the process of ancestral sequence reconstruction. Since many carbohydrate-active enzymes have highly conserved active sites, the strategy and their biomolecular basis will shield a new light for engineering carbohydrates hydrolase to produce specific oligosaccharides.

Electron spin modulation engineering in oxygen-involved electrocatalysis.

Electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reduction (OER) are regarded as the key reactions via the sustainable system (fuel cell and water splitting), respectively. In OER, the transition from singlet oxygen species to triplet oxygen molecules is involved, meanwhile the ORR involves the transition from triplet oxygen molecules to singlet oxygen species. However, in these processes, the number of unpaired electrons is not conserved, which is not thermodynamically favorable and creates an additional energy barrier. Fortunately, regulating the electrocatalysis by spin-state modulation enables a unique effect on the catalytic performance, but the current understanding on spin-state engineering for electro-catalyzing ORR and OER is still insufficient. Herein, this review summarized the in-spin engineering for the state-of-the-art ORR and OER electrocatalysts. It began by introducing engineering of spin-state to egfilling for ORR and OER process, and then moved to spin polarization and spin-pinning effect for OER process. Various designed strategies focusing on how to regulate the spin-state of the active center have been summarized up. The connectivity of the structures of typical ORR (e.g. metal-nitrogen-carbon) and OER (e.g. design strategies oxides, metal organic frameworks) catalysts depending on the spin level is also discussed. Finally, we present the outlook from the aspects of template catalysts, characterization methods, regulation strategies, theoretical calculations, which will further expand the possibility of better electrocatalytic performance through spin-state modulation. This review concluded some open suggestions and prospects, which are worthy of the community's future work.

Spatiotemporal variation characteristics of livestock manure nutrient in the soil environment of the Yangtze River Delta from 1980 to 2018.

The pollution problem caused by surplus livestock manure nutrient is becoming more and more serious; thus, analyzing characteristics of the temporal and spatial patterns of livestock manure nutrient and assessing the risks are extremely important. The pollution coefficient method was used to figure out the spatiotemporal variation characteristics of the nitrogen (N) and phosphorus (P) emissions of livestock manure nutrient in soil of the Yangtze River Delta from 1980 to 2018. High-risk areas for livestock manure pollution were determined by matching degree assessment between livestock manure nutrient supply and crop nutrient requirements. Clustering and principal component analysis were applied to select main control factors. The results found that the total discharge and manure N and P loads in animal manure nutrient showed an overall trend of increasing first and then decreasing in the Yangtze River Delta in the soil from 1980 to 2018. The center of manure N and P loads shifted from the central region to the northeastern and southwestern regions. There were four typical patterns for manure N emissions, the main control factors were meat production and primary industry. Meanwhile, the main control factors for the four typical patterns of manure P emissions were meat production and cultivated land area. This research provides a theoretical basis for the sustainable development of the livestock breeding industry and is of significance for promoting a balance between planting and breeding in the Yangtze River Delta.

Behaviors of 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB) in wheat seedlings: Bioaccumulation, biotransformation and ecotoxicity.

As a new alternative to perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB) has been currently used in industrial and consumer applications, which has been frequently detected in environment media. However, the behaviors of 6:2 FTAB in plants are still unclear. This study investigated the bioaccumulation, biotransformation and ecotoxicity of 6:2 FTAB in wheat (Triticum aestivum L.) by hydroponic exposure. 6:2 FTAB was easily taken up by roots with the root concentration factor (RCF) as high as 94.8, but difficult to be acropetally translocated in the shoots with the translocation factor (TF) as low as 0.058. Two intermediates and six terminal perfluorocarboxylic acid (PFCA) metabolites were detected in roots and shoots. The detected metabolites included 6:2 fluorotelomer sulfonic acid (6:2 FTSA), 6:2 fluorotelomer carboxylic acid (6:2 FTCA), perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), perfluorobutyric acid (PFBA), pentafluoropropionic acid (PFPrA) and trifluoroacetic acid (TFA), and 6:2 FTSA was the main metabolite. 6:2 FTAB significantly reduced the biomass of plant and prevented chlorophyll (Chl) accumulation, while caused no significant change in malondialdehyde (MDA) content. Significant reduction in glutathione (GSH) contents, excess production of reactive oxygen species (ROS), and obvious inhibition of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-s-transferase (GST) activities were observed, suggesting damage of antioxidant defense systems and failure to detoxication of 6:2 FTAB in wheat. These findings provide important knowledge for the fate of 6:2 FTAB in plants.

Concave Pt-Zn Nanocubes with High-Index Faceted Pt Skin as Highly Efficient Oxygen Reduction Catalyst.

High dosage of expensive Pt to catalyze the sluggish oxygen reduction reaction (ORR) on the cathode severely impedes the commercialization of proton exchange membrane fuel cells. Therefore, it is urgent to cut down the Pt catalyst by efficiently improving the ORR activity while maintaining high durability. Herein, magic concave Pt-Zn nanocubes with high-index faceted Pt skin (Pt78 Zn22 ) are proposed for high-efficiency catalysis toward proton exchange membrane fuel cells. These unique structural features endow the Pt-skin Pt78 Zn22 /KB with a mass activity of 1.18 mA µgPt -1 and a specific activity of 3.64 mA cm-2 for the ORR at 0.9 V (vs RHE). Meanwhile, the H2 -O2 fuel cell assembled by this catalyst delivers an ultrahigh peak power density of ≈1449 mW cm-2 . Both experiments and theoretical calculations show that the electronic structure of the surface is adjusted, thereby shortening the length of the Pt-Pt bond and reducing the adsorption energy of OH*/O* on the Pt surface. This work demonstrates the synergistic effect of the oxidation-resistant metal Zn and the construction of Pt-rich surface engineering. Also, it guides the future development of catalysts for their practical applications in energy conversion technologies and beyond.

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma.

SIMPLE SUMMARY: Clinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future. BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC. MATERIALS AND METHODS: Expressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses. RESULTS: LRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2. CONCLUSION: LRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.

Effects of two inhibitors of metabolic glutamate receptor 5 on expression of endogenous homer scaffold protein 1 in the auditory cortex of mice with tinnitus.

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.

Boosting Nitrogen Reduction to Ammonia on FeN4 Sites by Atomic Spin Regulation.

Understanding the relationship between the electronic state of active sites and N2 reduction reaction (NRR) performance is essential to explore efficient electrocatalysts. Herein, atomically dispersed Fe and Mo sites are designed and achieved in the form of well-defined FeN4 and MoN4 coordination in polyphthalocyanine (PPc) organic framework to investigate the influence of the spin state of FeN4 on NRR behavior. The neighboring MoN4 can regulate the spin state of Fe center in FeN4 from high-spin (dxy 2 dyz 1 dxz 1 d z 2 1 d x 2 - y 2 1 ) to medium-spin (dxy 2 dyz 2 dxz 1 d z 2 1 ), where the empty d orbitals and separate d electron favor the overlap of Fe 3d with the N 2p orbitals, more effectively activating N≡N triple bond. Theoretical modeling suggests that the NRR preferably takes place on FeN4 instead of MoN4 , and the transition of Fe spin state significantly lowers the energy barrier of the potential determining step, which is conducive to the first hydrogenation of N2 . As a result, FeMoPPc with medium-spin FeN4 exhibits 2.0 and 9.0 times higher Faradaic efficiency and 2.0 and 17.2 times higher NH3 yields for NRR than FePPc with high-spin FeN4 and MoPPc with MoN4 , respectively. These new insights may open up opportunities for exploiting efficient NRR electrocatalysts by atomically regulating the spin state of metal centers.

Applications of 3D Bio-Printing in Tissue Engineering and Biomedicine.

In recent years, 3D bio-printing technology has developed rapidly and become an advanced bio-manufacturing technology. At present, 3D bio-printing technology has been explored in the fields of tissue engineering, drug testing and screening, regenerative medicine and clinical disease research and has achieved many research results. Among them, the application of 3D bio-printing technology in tissue engineering has been widely concerned by researchers, and it contributing many breakthroughs in the preparation of tissue engineering scaffolds. In the future, it is possible to print fully functional tissues or organs by using 3D bio-printing technology which exhibiting great potential development prospects in th applications of organ transplantation and human body implants. It is expected to solve thebiomedical problems of organ shortage and repair of damaged tissues and organs. Besides,3Dbio-printing technology will benefit human beings in more fields. Therefore, this paper reviews the current applications, research progresses and limitations of 3D bio-printing technology in biomedical and life sciences, and discusses the main printing strategies of 3D bio-printing technology. And, the research emphases, possible development trends and suggestions of the application of 3D bio-printing are summarized to provide references for the application research of 3D bio-printing.

Design, Synthesis, and Antifungal Activity of Novel Longifolene-Derived Diacylhydrazine Compounds.

Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, 1H NMR, 13C NMR, electrospray mass spectrometry, and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated. As a result, some of them showed better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compound 5a had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against Physalospora piricola, Colletotrichum orbiculare, Alternaria solani, and Gibberella zeae, respectively, presenting excellent and broad-spectrum activity that deserved further study. Besides, a reasonable and effective three-dimensional structure-activity quantitative relationship model has been established. There was a significant positive correlation between the antifungal activity and the docking-based binding energy analyzed using Spearman's rank correlation algorithm. Also, the simulative binding pattern of the target compounds with SDH was investigated by molecular docking study. Furthermore, the diacylhydrazine and phenol groups of the target compounds were proposed to be the potential pharmacophores by frontier molecular orbital analysis.

Formation of perfluorocarboxylic acids (PFCAs) during the exposure of earthworms to 6:2 fluorotelomer sulfonic acid (6:2 FTSA).

6:2 fluorotelomer sulfonic acid (6:2 FTSA) is a novel perfluorooctane sulfonate (PFOS) alternative used globally in aqueous film forming foams (AFFFs). Although 6:2 FTSA has been recently detected in the environment, its fate in terrestrial invertebrates remains unclear. The uptake, elimination and biotransformation of 6:2 FTSA in earthworms (Eisenia fetida) were investigated after in vivo and in vitro exposure. 6:2 FTSA could be biodegraded by microorganisms in soil to trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA). The uptake rate constant (ku) and biota-to-soil accumulation factor (BSAF) of 6:2 FTSA in earthworms were 0.185 goc/gww/d and 0.685 goc/gww, respectively, indicating high bioaccumulative ability in earthworms. Five terminal perfluorocarboxylic acids (PFCAs) metabolites, including TFA, PFPrA, PFBA, PFPeA and PFHxA were observed in both in vivo and in vitro exposure tests, with TFA as the predominant metabolite. However, no perfluoroheptanoic acid (PFHpA) was observed in the present study. The elimination rate constants (ke) increased in the order: 6:2 FTSA (0.057/d) < TFA (0.058/d) < PFPrA (0.071/d) < PFBA (0.084/d) < PFHxA (0.182/d) < PFPeA (0.193/d). Biodegradation of 6:2 FTSA in the earthworm homogenates, cytolchrome P450 (CYP450) enzyme solutions and glutathione-s-transferase (GST) enzyme solutions fitted well with the first order kinetics. The biotransformation rate constants (k) were in the following order: homogenates (0.012/h) > CYP450 (0.009/h) > GST (0.007/h), implying that CYP450 and GST were involved in biotransformation of 6:2 FTSA in earthworms. This study provides important theoretical evidence for the fate of 6:2 FTSA in earthworms.

A species-specific miRNA participates in biomineralization by targeting CDS regions of Prisilkin-39 and ACCBP in Pinctada fucata.

Biomineralization is a sophisticated biological process precisely regulated by multiple molecules and pathways. Accumulating miRNAs have been identified in invertebrates but their functions in biomineralization are poorly studied. Here, an oyster species-specific miRNA, novel_miR_1 was found to regulate biomineralization in Pinctada fucata. Target prediction showed that novel_miR_1 could target Prisilkin-39 and ACCBP by binding to their coding sequences (CDS). Tissue distribution analysis revealed that the expression level of novel_miR_1 was highest in the mantle, which was a key tissue participating in biomineralization. Gain-of-function assay in vivo showed that biomineralization-related genes including Prisilkin-39 and ACCBP were down-regulated and shell inner surfaces of both prismatic and nacreous layer were disrupted after the over-expression of novel_miR_1, indicating its dual roles in biomineralization. Furthermore, the shell notching results indicated that novel_miR_1 was involved in shell regeneration. Dual-luciferase reporter assay in vitro demonstrated that novel_miR_1 directly suppressed Prisilkin-39 and ACCBP genes by binding to the CDS regions. Taken together, these results suggest that novel_miR_1 is a direct negative regulator to Prisilkin-39 and ACCBP and plays an indispensable and important role in biomineralization in both prismatic and nacreous layer of P. fucata.