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Supplementary Material 2

Supplementary Material 1

Label distribution learning (LDL) is an effective method to predict the label description degree (a.k.a. label distribution) of a sample. However, annotating label distribution (LD) for training samples is extremely costly. So recent studies often first use label enhancement (LE) to generate the estimated label distribution from the logical label and then apply external LDL algorithms on the recovered label distribution to predict the label distribution for unseen samples. But this step-wise manner overlooks the possible connections between LE and LDL. Moreover, the existing LE approaches may assign some description degrees to invalid labels. To solve the above problems, we propose a novel method to learn an LDL model directly from the logical label, which unifies LE and LDL into a joint model, and avoids the drawbacks of the previous LE methods. Extensive experiments on various datasets prove that the proposed approach can construct a reliable LDL model directly from the logical label, and produce more accurate label distribution than the state-of-the-art LE methods.

Ketoreductases have shown considerable potential as biocatalysts in the asymmetric synthesis of chiral alcohols. However, compared to the widely studied ketoreductases for chiral alcohols, limited knowledge is available about ketoreductases for efficient dynamic reductive kinetic resolution (DYRKR) of bulky α-amino β-keto esters. In this study, structure-guided rational direct evolution was applied to a ketoreductase (WTEA) from Exiguobacterium sp. F42 for the asymmetric reduction of bulky α-amino β-keto esters. A number of mutants were then obtained with remarkably improved activity toward various bulky α-amino β-keto esters with excellent stereoselectivity by performing structure-guided rational design. In particular, mutant M30 (W82L/F88V/V121A/A138L/R142M/A190V/S193A/Y201F/N204A) exhibited excellent stereoselectivity (>99% dr, >99% de) and high conversion (>99%) for six α-amino β-keto esters. Furthermore, novel and practical chemoenzymatic routes were developed for the synthesis of chloramphenicol and florfenicol, which featured the application of enzymatic DYRKR to establish the two stereocenters of amino alcohols 4-NO2-substituted (2S, 3R)-5b and 4-SO2Me-substituted (2S, 3R)-8b with > 99% dr, > 99% de and >99% conversion from 100 g L−1 α-amino β-keto esters 5a and 8a (highest substrate loading reported), respectively. Crystal structure and molecular dynamics studies revealed the potential molecular basis for activity improvement and the stereoselectivity control mechanism at the atomic level. These results provide important insights into the evolution of ketoreductases for the asymmetric synthesis of chiral vicinal amino alcohols and establish a solid foundation for further large-scale industrial applications in the future.

Micro-pumping and valving based on ferrofluid is a promising research area that offers novel solutions in many potential engineering and biomedical applications. In this paper, a novel electromagnetic actuated valve design based on ferrofluid action is presented. To date, traditional mechanical pumps and valves is replete with limiting features such as low on-off frequency limit, contact wear losses, and bulky size. However, due to the superparamagnetism and the high magnetic susceptibility of the ferromagnetic nanoparticles, ferrofluid can be actuated by magnetic field to perform fast-responsive, shape-controllable and small-scale valving actions. In this study, finite element models are built to analyze various design parameters including valve shape, valve dimensions, electromagnetic characteristic of ferrofluid and applied magnetic fields. An electromagnetic actuated ferrofluid valve is then designed and implemented. The valves are tested with switching frequency up to 250 Hz, and the valve’s diameter can be scaled down to 1 mm and beyond.

We first developed a novel and efficient chemoenzymatic process to prepare (S)-1-(pyridin-4-yl)-1,3-propanediol, a vital HepDirect prodrug intermediate, from inexpensive and commercially available ...

Additional file 1: Figure S1. Dry cell weights of SIPI12-34, ΔTetR1 and ΔTetR1/TetR1 at different times during the fermentation stage. Figure S2. The elimination of genomic DNA in obtained RNA of SIPI12-34 and ΔTetR1 were confirmed by PCR amplification using the primer pairs 16S1-F/R. Figure S3. The elimination of genomic DNA in obtained RNA of SIPI12-34 and SIPI12-34/TetR1 were confirmed by PCR amplification using the primer pairs 16S1-F/R. Figure S4. Acarbose production profiles of SIPI12-34 and SIPI12-34/dCas9-EMP were analyzed by HPLC. Figure S5. Dry cell weights of SIPI12-34 and SIPI12-34/dCas9-EMP at different times during the fermentation stage. Figure S6. The expression of genes encoding glycogen synthase derived from transcriptome sequencing. Figure S7. PCR validation of ΔGS and SIPI12-34. Figure S8. Dry cell weights of SIPI12-34 and ΔGS/glgP at different times during the fermentation stage. Figure S9. Dry cell weights of SIPI12-34 and SIPI2207 at different times during the fermentation stage. Figure S10. Dry cell weights of SIPI2207 with addition of different sugars during the fermentation stage. Figure S11. Acarbose production profiles of SIPI12-34 and SIPI12-34/acbD were analyzed by HPLC.

Background Coronary heart disease (CHD), sarcopenia and depression are common disorders that markedly impair quality of life and impose a huge financial burden on society. They are also frequently comorbid, exacerbating condition and worsening prognosis. This study aimed to investigate the additive effects of CHD and sarcopenia on the risk of new onset depressive symptoms in older adults. Methods The prospective cohort study comprised 897 Chinese community-dwelling participants who were aged 60 years and older (386 men; mean age 66.9 ± 5.9 years) without depressive symptoms at baseline, recruited from Chadian of Tianjin, China. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) criteria. CHD was identified via medical records or new diagnosed by at least two physicians. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) ≥11. Longitudinal data on new onset depressive symptoms were collected up to 12 months after baseline. Results We found that 103 (11.5%) of the 897 participants without depressive symptoms at baseline had developed depressive symptoms. Participants were classified into mutually exclusive groups based on sarcopenia status and CHD: normal, CHD alone, sarcopenia alone, and co-occurring groups. A logistic regression showed that the CHD alone [odd ratios (OR) = 1.78, 95% confidence interval (CI) = 1.05–3.02], sarcopenia alone (OR = 2.79, 95% CI = 1.26–6.22), and co-occurring (OR = 7.19, 95% CI = 2.75–18.81) had higher risk of depressive symptoms than the normal group after adjusting for the covariates. Conclusions CHD and sarcopenia synergistically increase the risk of new onset depressive symptoms in older adults. Thus, older adults may require early detection, and appropriate interventions should be implemented.

(S)-2-Chloro-1-(2,4-dichlorophenyl) ethanol (3) is a chiral intermediate in the synthesis of luliconazole ((R)-E-1). Here, we report a novel biopreparation of 3 by bioreduction of 2-chloro-1-(2,4-d...

The potential negative effects of perfluoroalkyl substances (PFASs) discharged into aquatic environments are drawing increasing attention. However, little research has been undertaken on PFASs in wastewater from electroplating industrial parks. In this study, the concentration profiles and geographical distribution of 11 PFASs were analyzed in water samples collected from different production workshops and an artificial landscaped lake. The total concentrations of PFASs (Σ11PFASs) at various points in the production drainage system range from 229.5 to 5410.6 ng/L, and are mainly contributed by nickel plating, pickling, and the cyanide bright silver plating procedure, which correspond to cyanide-containing and acid-alkali wastewater conditioning tanks. Wastewater treatment by oxidation and precipitation removed 52.6% and 20% of PFASs, respectively. Σ11PFASs in effluents is about 538 ng/L, which consists of perfluorooctanoic acid (PFOA, 430.5 ng/L), followed by perfluorooctane sulfonate (PFOS, 35.27 ng/L), perfluorohexane sulfonate (PFHxS, 28.05 ng/L), and perfluorohexanoic acid (PFHxA, 18.3 ng/L). Principal component analysis suggests that the Σ11PFASs in electroplating wastewater is very high and short-chain (C4–C8) PFASs have high detection and contribution rates. As a result, much attention should be paid to the increase in short-chain substitution effects and pollution around the factory area.

(R)-[3,5-bis(trifluoromethyl) phenyl] ethanol [(R)-3,5-BTPE] is a crucial chiral intermediate for the synthesis of the NK-1 receptor antagonists aprepitant, rolapitant and fosaprepitant. The carbonyl reductase KR01 from Leifsonia sp. S749, discovered by protein sequence alignment, could convert 3′,5′-bis(trifluoromethyl) acetophenone (3,5-BTAP) into (R)-3,5-BTPE with excellent activity and enantioselectivity. In order to enhance the conversion efficiency at high substrate concentrations, the reaction conditions were optimized by response surface analysis. The results showed that 600 g/L 3,5-BTAP was bioreduced to (R)-3,5-BTPE (> 99.9% enantiomeric excess) by the recombinant Escherichia coli/pET-28a (+)-KR01 whole cells, with a 98.3% conversion and 59 g/L/h productivity under the optimized reaction conditions. In addition, the recombinant E. coli cells could be repeatedly used up to seven times in the reaction mixture containing 90% isopropanol (IPA). This is the highest substrate loading and productivity for the bioreduction of 3,5-BTAP by carbonyl reductase ever reported, and this method represents an efficient and cost-effective process for production of (R)-3,5-BTPE.

The momentum method was considered to be not applicable for a fine grid adjacent to the diffuser. However, the reason underlying this phenomenon has not been clarified until now. This paper explains this issue from the viewpoint of discretization. The momentum equation is integrated in the first cell adjacent to the diffuser and is expressed as the diffuser-related term and the diffuser nonrelated term. The direct momentum method and the convective-flux momentum method use different diffuser-related terms. A large error may be introduced for the convective-flux momentum method when the first grid interval adjacent to the diffuser is very small. The total-flux momentum method is presented to include both the convective flux and the diffusion flux in the momentum source. Good agreement between the total-flux momentum method and experiment is obtained. The total-flux momentum method helps to minimize the computational error and facilitates the determination of an optimal grid.

(S)-2-Chloro-1-(3,4-difluorophenyl)ethanol (1) is a vital chiral intermediate for the synthesis of Ticagrelor—an effective treatment for acute coronary syndromes. A ketoreductase (KRED) KR-01 in our KRED library was screened to transform 2-chloro-1-(3,4-difluorophenyl)ethanone (2) into the chiral alcohol 1. During process optimization, the bioreduction procedure was performed at a substrate concentration of 500 g/L, giving a near 100% conversion with >99.9% ee. The product 1 was directly obtained by extraction and can be used for the synthesis of (1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxylic acid ethyl ester (3) with a yield of 98% and >99.9% de, greatly simplifying the original process operation and reducing the safety risk. This process is green and environmentally sound with high productivity of biocatalysis and a space–time yield of 145.8 mmol/L/h. It has an opportunity to be very useful in industrial applications. Additional studies have indicated that KR-01 can also be used to prepare (R)-1-(...

Commonly, the strong heterogeneity leads to poorer sweep efficiency for poor reservoir. So, liquid production rate optimization was often used to improve development effect, especially liquid production rate increasing in high water cut stage. However, the quantitative relationship between the rising law of water cut and the main control factors is not clear, which results in the uncertainty of water cut changing after liquid increasing. This paper proposed a theoretical prediction model of water cut presenting the correlations between water cut and formation parameters, fluid property parameters, relative permeability parameters and production control conditions. Furthermore, the water cut rising law is theoretically divided into three types (continuous rising type, stable type and step type). Moreover, the theoretical equation of water cut change after liquid increasing is established, and the critical mathematical conditions were clarified for different kinds of water cut changing law such as water cut rising, unchanged or decreasing in complex multi-layer reservoirs. Then, oil rate increment and liquid rate changing can be predicted quantitatively further. The proposed method could be used for the working system optimization, stimulation optimization and development plan adjustment. It has been proved to have a high accuracy based on the actual dynamic data.

The research object of this paper is KFC which acts as the typical representative of catering in China. Based on the foundation of the previous studies, this paper defines the concepts of psychological contracts on the consumer-brand relationship under the marketing scenario, and builds up a model, and discusses the dimensions of the psychological contracts. Results offer theoretical reference for the Chinese enterprise in brand management under the globalization background.