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Objective. To explore the mechanism of electroacupuncture stimulation of the hand-taiyin meridian in regulating the molecular network of rats with cerebral ischemia-reperfusion injury based on transcriptomics. Methods. Male SD rats were randomly divided into sham operation group, model group, and electroacupuncture (EA) group. Middle cerebral artery embolization/reperfusion injury (MCAO/R) was used to establish the model group and EA group. The sham operation group only performed sham operation without modeling and any intervention, and the model group was bound daily. The EA group received electroacupuncture to stimulate the acupoints of hand-taiyin meridian for 14 days. Then, neurological scores, pathomorphological observations, and Tunel staining were performed. Finally, the affected hippocampus of the rat was used for transcriptome sequencing and RT-PCR detection. Results. After electroacupuncture intervention in rats, neurological function scores were improved, and neuronal apoptosis was reduced. The results of transcriptomics showed that a total of 1097 differentially expressed genes were obtained, of which 422 were upregulated and 675 were downregulated. The bioinformatics analysis showed that those differentially expressed genes were related to axon development, neuron projection development, neuron projection morphogenesis, plasma membrane cell projection morphogenesis, cell part morphogenesis, notch signaling pathway, long-term potentiation, MAPK signaling pathway, Hedgehog signaling pathway, and so on. The results of RT-PCR showed that Caspase 9 mRNA increased and BDNF, Grin2a, and PlexinD1 mRNA decreased after electroacupuncture intervention P < 0.05 . Conclusion. Electroacupuncture intervention on hand-taiyin meridian may reduce neurological function scores, inhibit neuron apoptosis, and enhance neuronal repair neuroreparation in MCAO/R rats, which may be related to the regulation of genes such as Caspase 9, BDNF, Grin2a, and PlexinD1.

Although personalized automatic speech recognition (ASR) models have recently been designed to recognize even severely impaired speech, model performance may degrade over time for persons with degenerating speech. The aims of this study were to (1) analyze the change of performance of ASR over time in individuals with degrading speech, and (2) explore mitigation strategies to optimize recognition throughout disease progression. Speech was recorded by four individuals with degrading speech due to amyotrophic lateral sclerosis (ALS). Word error rates (WER) across recording sessions were computed for three ASR models: Unadapted Speaker Independent (U-SI), Adapted Speaker Independent (A-SI), and Adapted Speaker Dependent (A-SD or personalized). The performance of all three models degraded significantly over time as speech became more impaired, but the performance of the A-SD model improved markedly when it was updated with recordings from the severe stages of speech progression. Recording additional utterances early in the disease before speech degraded significantly did not improve the performance of A-SD models. Overall, our findings emphasize the importance of continuous recording (and model retraining) when providing personalized models for individuals with progressive speech impairments., Comment: Submitted to ICASSP 2023

Actinide complexes, which could enable the electrocatalytic H

Background༚Recently, there has been increasing evidence that acupuncture as a kind of Traditional Chinese therapeutic method is significantly effective and safe way to treat Alzheimer’s disease (AD). This study provides supporting evidence and mechanism explanation of the therapeutic benefits of EA in the treatment of AD. Method, In this study, we used tandem mass tagged (TMT) quantitative proteomics and bioinformatics analysis to seek core differentially expressed proteins (DEPs) in the typical pathways. And the DEPs were validated by parallel reaction monitoring (PRM). Results, weidentified 211 proteins thatwere differentiallyexpressed among the different groups. Finally, we identified the following key DEPs:A0A0G2QC31(protein tyrosine phosphatase, PTP) and P31647 (Sodium- and chloride-dependent GABA transporter 3, GAT3), which are enriched in the synaptic vesicle pathway and glutamatergic synaptic pathway respectively.Validation of protein expression by PRM, it was found that the downregulation of GAT3 and PTP in the hippocampus of AD rats after EA treatment. These key proteins and related signaling pathways might be the possible mechanisms of AD treatment. Conclusion, EA may be providing a neuroprotective effect in cognitive disorders through glutamate synaptic signaling pathway and synaptic vesicle signalingpathway in Aβ1–42-induced AD rat model.

Three-dimensional (3D) printing of ceramics has attracted increasing attention in various fields. However, the pyrolysis of organic components used for binding or polymerization in 3D printing commonly causes a large shrinkage (up to 30 %–40 %), high porosity, and cracking or deformation, severely limiting practical applications. In this study, 3D printing of Al2O3 ceramic architectures with ultra-low shrinkage is realized by introducing inorganic binder aluminum dihydrogen phosphate (Al(H2PO4)3, AP) as a ceramic precursor. Compared to organic binders, the inorganic AP binder can undergo crystallization conversion, which reduces mass loss during sintering at high temperatures, resulting in low shrinkage. Moreover, AP can be used as a rheological modifier to regulate the printability of the ceramic ink for direct ink writing of Al2O3 ceramic architectures, such as wood-piled scaffolds, honeycomb structures, and tubes with high fidelity. The resultant Al2O3 structural ceramics sintered at 1250 °C exhibit good mechanical performance and structural integrity. Most importantly, the linear shrinkage of the printed ceramics is less than 5 %, which is several times lower than that of ceramics with organic binders. This study provides a viable strategy for fabricating high-performance ceramic architectures with good dimensional fidelity for practical applications.

We developed dysarthric speech intelligibility classifiers on 551,176 disordered speech samples contributed by a diverse set of 468 speakers, with a range of self-reported speaking disorders and rated for their overall intelligibility on a five-point scale. We trained three models following different deep learning approaches and evaluated them on ~94K utterances from 100 speakers. We further found the models to generalize well (without further training) on the TORGO database (100% accuracy), UASpeech (0.93 correlation), ALS-TDI PMP (0.81 AUC) datasets as well as on a dataset of realistic unprompted speech we gathered (106 dysarthric and 76 control speakers,~2300 samples)., Comment: ICASSP 2023 camera-ready

Alzheimer disease (AD) is a common cause of dementia, and there are still a lack of treatment options to reverse or prevent disease progression. Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict systematic review and network meta-analysis to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD.From the inception to February 2023, the Embase, Latin American and Caribbean Health Sciences Literature, Medline, the Cochrane Collaboration's Controlled Clinical Trials, Scopus, China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure, and Australian Medical Index will be searched using the key phrases "acupuncture," "warm needling," "electroacupuncture," "Alzheimer disease," and "cohort" for all relevant studies. Quality assessment of all studies included in this review will be independently assessed by 2 reviewers using the Cochrane Collaborations tool. When significant heterogeneity is indicated, we will find the source of heterogeneity by subgroup or sensitivity analysis.This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients. The results of this study will verify whether the efficacy of acupuncture in the treatment of AD belongs to the placebo effect, which will also provide a reference for the clinical use of acupuncture combined with Western medicine in the treatment of AD.

Background (−)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (−)-Perillamine, as derived from (−)-limonene, is a highly useful synthon for constructing more complicated and functionally relevant chemicals. Aim We aimed to report a more sustainable and more efficient method for the regiospecific C–H amination of (−)-limonene into (−)-perillamine. Results Here, we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (−)-limonene into (−)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (−)-limonene was smoothly converted into 5.4 mM (−)-perillamine in a one-pot two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C–H bond of (−)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.

Artificial biorefinery of oleic acid into 1,10-decanedioic acid represents a revolutionizing route to the sustainable production of chemically difficult-to-make bifunctional chemicals. However, the carbon atom economy is extremely low (56%) due to the formation of unifunctional

Junyu Zheng, Cong Li, Zining Zhu, Fengming Yang, Xiaoming Wang, Pan Jiang, Feng Yan Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, 210009, People’s Republic of ChinaCorrespondence: Feng Yan, Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, 42 Baiziting Road, Nanjing, 210009, Jiangsu, People’s Republic of China, Tel +86-13851641895, Email yanfeng@jszlyy.com.cnBackground: Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC.Methods: Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR. In vitro functional assays were used to evaluate the influences of tsRNAs on GC cells. The potential mechanisms underlying tsRNAs were explored using bioinformatics analysis,RT-qPCR, RNA immunoprecipitation assays and Western blot.Results: We found that tiRNA-Val-CAC-001 was downregulated in GC tissues and cells, and demonstrated that tiRNA-Val-CAC-001 was a tsRNA sheared from mature tRNA-Val and mainly localized in the cytoplasm. tiRNA-Val-CAC-001 overexpression inhibited metastasis and proliferation but promoted apoptosis of GC cells; nevertheless, tiRNA-Val-CAC-001 knockdown increased metastasis and proliferation and reduced apoptosis (P< 0.05). GO and KEGG analyses indicated tiRNA-Val-CAC-001 may exert its effects via Wnt/β-catenin signaling pathway by targeting LRP6. Following experiments showed that tiRNA-Val-CAC-001 could downregulated the protein levels of LRP6 and β-catenin, but up-regulated p-β-catenin, which confirmed the findings in bioinformatics analysis.Conclusion: In conclusion, tiRNA-Val-CAC-001 works as a cancer suppressor in GC by targeting LRP6 via Wnt/β-catenin signaling pathway. tiRNA-Val-CAC-001 may serve as a therapy target and a biomarker of GC in the future.Key Points: tiRNA-Val-CAC-001 is downregulated in gastric cancer tissues and cell lines, tiRNA-Val-CAC-001 has potential to become a novel diagnostic biomarker in gastric cancer, and tiRNA-Val-CAC-001 regulates gastric cancer cells by targeting LRP6.Keywords: gastric cancer, tRNA-derived-fragments, LRP6, metastasis, proliferation, apoptosis

Cyclin D2 (CCND2) is abnormally overexpressed in many tumor types and has been associated with tumor cell proliferation. Although the important role of miR-1297 is well established, the molecular mechanism between CCND2 and miR-1297 in osteosarcoma (OS) has not been determined. In the present study, we found CCND2 was highly expressed in OS cells, and its downregulation suppressed cell proliferation, resulting in G1 phase cell cycle arrest. In contrast, miR-1297 was lowly expressed in OS compared to normal tissue. Several data platforms predicted that CCND2 was a target of miR-1297, which was validated by a dual-luciferase reporter assay that revealed miR-1297 could bind with CCND2-3'UTR. miR-1297 overexpression greatly inhibited CCND2 protein expression and exerted the same phenotypic effect as CCND2 downregulation in OS cells. Furthermore, miR-1297 inhibition could also be rescued by CCND2. Nude mice injected cells stable overexpressing miR-1297 OS cells showed lower size and tumor weight. Moreover, lower fluorescence activity recorded by in vivo imaging system and bone erosion revealed by microCT in the miR-1297 group demonstrated miR-1297 inhibited OS tumor growth via CCND2. Our findings demonstrated that miR-1297 can inhibit proliferation and tumor growth in OS by directly targeting CCND2, which indicates that miR-1297 may represent a novel therapeutic target for OS.

Radiation dosimeters displaying conspicuous response of irradiance are highly desirable, owing to the growing demand of monitoring high-energy radiation and environmental exposure. Herein, we present a case of dosimetry based on a discrete nanocluster, [Th6(OH)4(O)4(H2O)6](TPC)8(HCOO)4∙4DMF∙H2O (Th-SINAP-100), by judiciously incorporating heavy Th6 polynuclear centers as radiation attenuator and organic linkers as photo-responsive sensor. Interestingly, dual-module photochromic transitions upon multiple external stimuli including UV, β-ray, and γ-ray are integrated into this single material. The striking color change, and more significantly, the visible color transition of luminescence in response to accumulating radiation dose allow an on-site quantitative platform for naked-eye detection of ionization radiations over a broad range (1–80 kGy). Single crystal X-ray diffraction and density functional theory calculations reveal that the dual-module photochromism can be attributed to the π(TPC) → π*(TPC) intermolecular charge transfer driven by enhanced π-π stacking interaction between the adjacent TPC moieties upon irradiation., Radiation dosimeters that measure ionizing radiations over a broad range and allow for direct readout are desirable. Here, the authors present a dual-mode photochromic thorium-based metal-organic nanocluster that enables direct visible colorimetric dosimetry of UV, β-ray, and γ-ray radiation.

A series of hetero-bimetallic actinide complexes of the Schiff-base polypyrrolic macrocycle (L), featuring cation-cation interactions (CCIs), were systematically investigated using relativistic density functional theory (DFT). The tetrahydrofuran (THF) solvated complex [(THF)(OUVIOUIV)(THF)(L)]2+ has high reaction free energy (ΔrG), and its replacement with electron-donating iodine promotes the reaction thermodynamics to obtain uranyl iodide [(I)(OUVIOUIV)(I)(L)]2+ (UVI-UIV). Retaining this coordination geometry, calculations have been extended to other An(IV) (An = Th, Pa, Np, Pu), i.e., for the substitution of U(IV) to obtain UVI-AnIV. As a consequence, the reaction free energy is appreciably lowered, suggesting the thermodynamic feasibility for the experimental synthesis of these bimetallic complexes. Among all UVI-AnIV, the electron-spin density and high-lying occupied orbitals of UVI-PaIV show a large extent of electron transfer from electron-rich Pa(IV) to electron-deficient U(VI), leading to a more stable UV-PaV oxidation state. Additionally, the shortest bond distance and the comparatively negative Eint of the Pa-Oendo bond suggest more positive and negative charges (Q) of Pa and endo-oxo atoms, respectively. As a result of the enhanced Pa-Oendo bond and strong CCI in UVI-PaIV along with the corresponding lowest reaction free energy among all of the optimized complexes, uranyl species is a better candidate for the experimental synthesis in the ultimate context of environmental remediation.

Introducing the hierarchy into cellular materials has attracted increasing attention in the effort to pursue improved absorbed-energy abilities and impact resistance. In this paper, the dynamic crushing properties and energy absorption capacities of joint-based hierarchical honeycombs with different topologies were explored by means of explicit dynamic finite element (FE) analysis using ANSYS/LS-DYNA. Four types of joint-based hierarchical honeycombs with uniform cell-wall thickness were firstly constructed by substituting each vertex of regular honeycombs with a smaller self-similar cell (hexagon or square). The respective influences of hierarchical parameters and impact velocities on in-plane dynamic deformation modes, mechanical characteristic and energy absorption of joint-based hierarchical honeycombs were discussed. Research results showed that the hierarchy had a far greater influence on the in-plane deformation modes of honeycombs. Compared with regular honeycombs, the dynamic plateau stress and specific energy absorption of joint-based hierarchical honeycombs can be improved if the proper hierarchical parameters were chosen. Adding the joint-based hierarchy into regular honeycombs can enhance the crushing stress efficiency (CSE) of the specimens. In addition, by introducing a non-dimensional dynamic sensitivity index, the dynamic shock enhancement of hierarchical honeycombs was also investigated. These researches are useful for the multi-objective dynamic optimization design and controllable properties of cellular materials.

To date, the experimental studies on Nd-based metallofullerenes are only limited to spectroscopic characterizations. In this work, the molecular structures of Nd@C82(I,II) isomers, including the isomeric symmetry of the C cage and the position of endohedral Nd atom, as well as their unique two-dimensional (2D)-layered crystallographic packing structures were initially and unambiguously elucidated, based on the X-ray structural analyses of the cocrystals of Nd@C82(I) or Nd@C82(II) with cocrystallizing agent decapyrrylcorannulene (DPC). In the V-shaped unit cell, the endohedral Nd atom prefers a site as far away from the DPC molecules as possible because of the unevenly distributed charge on the C cage mainly related to the charge transfers from the endohedral Nd atom, cocrystallizing agent DPC, and solvent toluene molecules to the C82 cage. Apart from charge transfers, multiple C-H···π intermolecular interactions are also confirmed to play important roles both for the orientation of the C cage correlated with the preferential sites of the endohedral Nd atom and for the 2D-layered packing structures within the cocrystals. Density functional theory computations offered theoretical support for the molecular structures of Nd@C82(I,II) isomers, the valence of the endohedral Nd atom (between II+ and III+), and the global ground state, i.e., the Nd@C2v(9)-C82 isomer in the quintet state.

Oxidoreductase-mediated biotransformation often requires consumption of a secondary sacrificial co-substrate and an additional auxiliary enzyme to drive the cofactor regeneration, which results in generation of unwanted by-product. Herein, we report a highly atom-economic self-sufficient hydride-shuttling cascade to concurrently obtain two pharmaceutically important building blocks (7,12-dioxo-lithocholic acid and L-tert-leucine) in which oxidation of cholic acid (CA) and reductive amination of trimethylpyruvic acid were integrated for redox self-recycling. In this cascade, the cofactor acts as a hydride shuttle that interconnects the two synthetically relevant reactions at the cost of only inorganic ammonium as the sacrificial agent and generates water as the greenest by-product. The preparative biotransformation using a whole-cell biocatalyst in the absence of any exogenous cofactor displayed a space–time yield of 768 g L−1 d−1 and a total turnover number (TTN) of 20 363 for NAD+ recycling. This represents the highest cofactor TTN reported to date for the bio-oxidation of CA, indicating the great potential of this cofactor and redox self-sufficient bioprocess for cost-effective and sustainable biomanufacturing of high-value-added products.

The massive consumption of fossil energy forces people to find new sources of energy. Syngas fermentation has become a hot research field as its high potential in renewable energy production and sustainable development. In this study, trophic anaerobic acetogen Morella thermoacetica was successfully immobilized by calcium alginate embedding method. The ability of the immobilized cells on production of acetic acid through syngas fermentation was compared in both airlift and bubble column bioreactors. The bubble column bioreactor was selected as the better type of bioreactor. The production of acetic acid reached 32.3 g·L−1 in bubble column bioreactor with a space–time yield of 2.13 g·L−1·d−1. The immobilized acetogen could be efficiently reused without significant lag period, even if exposed to air for a short time. A semi-continuous syngas fermentation was performed using immobilized cells, with an average space–time acetic acid yield of 3.20 g·L−1·d−1. After 30 days of fermentation, no significant decrease of the acetic acid production rate was observed.

Due to the powerful reducing ability of the metal active site, low-valent uranium complexes show remarkable performance in activating thermodynamically stable and kinetically inert small molecules. In this work, experimentally known uranium metallocenes [Cp3U]z (z = 0 and +1) were intensively studied using relativistic density functional theory for their activation of small molecules (X = CO2, N2, CO and NO). Regardless of whether z = 0 or +1, a weak double bond was realized between uranium and NO, which is in agreement with a previous study; a weak single bond with the dative nature was assigned to other small-molecule uranium adducts. A general order for the uranium–small molecule bond strength, NO > CO > N2 > CO2, has been built, the trend being exactly the same as the computed reduction potentials. These are corroborated by energetics and experimental results that (i) analogues of the first three [Cp3U(X)] adducts were crystallographically identified but the one of [Cp3U(CO2)] was not, and (ii) much higher X gas pressure was required to synthesize [Cp3U(N2)] than for [Cp3U(CO)]. Additionally, the experimentally inaccessible CO2 adduct was rationalized using thermodynamic and kinetic calculations as well as geometric/electronic properties and bonding analyses.

Optically pure (R)-γ- and (R)-δ-lactones can be prepared by intramolecular cyclization of chiral hydroxy acids/esters reduced asymmetrically from γ- and δ-keto acids/esters using Saccharomyces cerevisiae (S. cerevisiae) as a whole-cell biocatalyst. However, some of the enzymes catalyzing these reactions in S. cerevisiae are still unknown up to date. In this report, two carbonyl reductases, OdCR1 and OdCR2, were successfully discovered, and cloned from S. cerevisiae using a genome-mining approach, and overexpressed in Escherichia coli (E. coli). Compared with OdCR1, OdCR2 can reduce 4-oxodecanoic acid and 5-oxodecanoic acid asymmetrically with higher stereoselectivity, generating (R)-γ-decalactone (99% ee) and (R)-δ-decalactone (98% ee) in 85% and 92% yields, respectively. This is the first report of native enzymes from S. cerevisiae for the enzymatic synthesis of chiral γ- and δ-lactones which is of wide uses in food and cosmetic industries.

Due to its good properties and low cost, melamine formaldehyde foam has been widely used in cars, furniture and construction. However, how to recycle the spent foam still remains challenging for scientists. In this work, a new method was designed to prepare N-doped carbon dot (NCD) materials by calcining sodium lignin sulfonate/melamine formaldehyde foam (LSMF) via one step. TEM, IR and XPS were used to characterize the structure and morphology of newly-synthesized NCDs. It is shown that carbon powder is obtainable by calcination. Since it derives from the collapse of the foam structure of LSMF, the carbon powder can almost completely dissolve in deionized water. The particle size ranges from 5 to 20 nm. The fluorescence properties of NCDs were studied by fluorescence spectroscopy. A strong emission has been detected at 580 nm with the quantum yield of 2.94%. When applying NCDs to detect various metal ions, there is a significant fluorescence quenching effect and good selectivity for Fe3+. The mechanism has been hypothesised. Our study provides a method for productive preparation of NCDs from spent foam.

Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 (PpBVMO), a novel BVMO from Gordonia sihwensis (GsBVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant (kcat /KM ) 8.9-fold to 484 s-1 mM-1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant GsBVMOC308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into 9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5 g L-1 d-1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.

To explore the innovative uranyl(V) complexes by deeply understanding their coordination stability, relativistic density functional theory calculations have been performed to investigate the experimentally reported [(py)(R2AlOUVO)(py)(H2L)] [R = Me (1), iBu (2)] and [{(py)3MOUVO}(py)(H2L)] [M = Li (3), Na (4), K (5)] and their uranyl(VI) counterparts. Structural and topological analyses along with transformation-reaction energies and redox potentials were systematically studied. Geometrical and quantum theory of atoms in molecules analyses implied a linear U-Oexo-M feature in 1-3 and a bent one in 4 and 5. The calculated free energies (ΔrG) of reactions transforming 1/2 into 3/4/5 confirmed a higher stability of the latter ones, which were further corroborated by their reduction potentials (E0). The E0 value of 5 versus uranyl(VI) is close to its experimental value, particularly in solvation with spin-orbit coupling. The highest occupied and lowest unoccupied molecular orbitals of uranyl(V) and uranyl(VI) have predominant U(5fδ) character. Compared to mononuclear uranyl(VI), the coordination of aluminum and alkali metals to uranyl exo-oxo significantly contributes to the stabilization of uranyl(V) by altering the E0 value from -1.59 to -0.85, -0.91, -1.33, -1.50, and -1.46 V, respectively. The calculation results show a more positive E0 than that of the precursor 6VI/6 without exo-oxo coordination. The calculated E0 values of 3-5 are certainly more negative than those of 1 and 2. The alkali metals were found to activate U═O bonds more easily/readily than aluminum by coordination to the exo-oxo atom. In brief, the uranyl exo-oxo cation-cation-interaction enhanced the reduction ability from its uranyl(VI) analogue and raised the stability of the UV center.

Background (−)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (−)-Perillamine, as derived from (−)-limonene, is such a useful synthon for constructing more complicated and functionally relevant chemicals. Aim We aimed to report a more sustainable and more efficient method for the regiospecific C-H amination of (−)-limonene into (−)-perillamine. Results Here we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (−)-limonene into (−)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (−)-limonene was smoothly converted into 5.4 mM (−)-perillamine in a one-pot-two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C-H bond of (−)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.

Background β-Nicotinamide mononucleotide (NMN) is the direct precursor of nicotinamide coenzymes such as NAD+ and NADP+, which are widely applied in industrial biocatalysis especially involving cofactor-dependent oxidoreductases. Moreover, NMN is a promising candidate for medical uses since it is considered to be beneficial for improving health of aged people who usually suffer from an insufficient level of NAD+. To date, various methods have been developed for the synthesis of NMN. Chemical phosphorylation of nicotinamide riboside (NR) to NMN depends on excessive phosphine oxychloride and delicate temperature control, while fermentation of NMN is limited by low product titers, making it unsuitable for industrial-scale NMN production. As a result, the more efficient synthesis process of NMN is still challenging. Aim This work attempted to construct an eco-friendly and cost-effective biocatalytic process for transforming the chemically synthesized NR into the highly value-added NMN. Results A new nicotinamide riboside kinase (Klm-NRK) was identified from Kluyveromyces marxianus. The specific activity of purified Klm-NRK was 7.9 U·mg–1 protein, ranking the highest record among the reported NRKs. The optimal pH of Klm-NRK was 7.0 in potassium phosphate buffer. The purified Klm-NRK retained a half activity after 7.29 h at 50 °C. The catalytic efficiencies (kcat/KM) toward ATP and nicotinamide riboside (NR) were 57.4 s−1·mM−1 and 84.4 s−1·mM−1, respectively. In the presence of an external ATP regeneration system (AcK/AcP), as much as 100 g·L–1 of NR could be completely phosphorylated to NMN in 8 h with Klm-NRK, achieving a molar isolation yield of 84.2% and a space–time yield of 281 g·L−1·day−1. These inspiring results indicated that Klm-NRK is a promising biocatalyst which provides an efficient approach for the bio-manufacturing of NMN in a high titer. Graphical Abstract

3D printing of hydrogels with high intrinsic mechanical performance has significant applications in many fields yet has been proven to be a fundamental challenge. Here, 3D printing of ultrahigh str...

Catalysis operated on supported single metal atom is considered as one of the vital efforts for chemical and energy conversion. Despite the enormous amount of research on single transition metal (TM) enhanced graphdiyne (GDY) material, its modification with slightly depleted uranium remains unexplored. Herein, we conducted relativistic density functional theory (DFT) calculations for the accumulation of atomic uranium inside size-suitable GDY pore. The stability of graphdiyne-uranium (GDY-U) is corroborated in terms of short U–C bond distances (2.34–2.44 A), with local depletion of charge and greater U(5f)-C(p) molecular orbital overlap. The magnificent structural and electronic properties of GDY-U system qualify it for the investigation of hydrogen evolution reaction (HER). The HER performance of all exposed sites, including central metal atom and four dissimilarly coordinated acetylenic carbons has been examined and compared with that of pure GDY. As the overall HER interfacial descriptor, free energy change of the intermediate state (ΔGH∗) at the central metal surface of GDY-U was found to be most favorable (0.153 eV) amongst all sites and far superior to those of pure GDY. In addition to the uranium surface, the coordinated carbons also show improved HER activity, indicating the enhancement of the system upon metal insertion. The calculated ΔGH∗ of the GDY-U system here is comparable to some of the recently reported GDY-TM materials, suggesting that atomic uranium could be an exceptional alternative for applied common catalysts.

Osteoarthritis (OA) is a non-inflammatory degenerative disease, with progressive damages on the articular cartilages. In recent years, researchers have paid many efforts in the diagnostics and treatments of OA. However, no effective therapeutic method has been revealed to help inhibit the development of OA. Herein, we studied the roles and associations of PCAT-1 and miR-27-3p in the pathogenesis OA. OA articular cartilages and healthy articular cartilages were isolated for investigation. The chondrocytes were isolated from articular cartilage samples. QRT-PCR and western blotting were used for the detection of expression of genes and proteins. cell Titer 96® AQueous one proliferation kit was applied for detect cell viability of Chondrocytes transfected with negative control vector, pcDNA3.1 PCAT-1 plasmid or siRNA against PCAT-1. RNA pull-down assays and Luciferase reporter assay were used to confirm the connection. SPSS 17.0 was employed for statistical analysis. We found that the expressions of PCAT-1 were up-regulated in OA chondrocytes compared with normal chondrocytes. si-PCAT-1 suppressed apoptotic OA chondrocytes. Over-expression of PCAT-1 enhanced the apoptosis of normal chondrocytes. In addition, the online database and luciferase assay confirmed that PCAT-1 could directly target miR-27b-3p. PCAT-1 could promote the apoptosis of OA and normal chondrocytes through binding with miR-27b-3p. Based on the comparisons and analysis, we could conclude that lncRNA PCAT-1 regulated the apoptosis of chondrocytes through sponging miR-27b-3p in OA. PCAT-1 has potential values to act as a new therapeutic target for OA patients.

The lignin amine (LA) was exploited to prepare dually N/S-doped carbon (NSC), which was endowed with intriguing porous structure by Fe3O4 template. N and S elements, originating from LA, are doped into the materials. NSC possesses diverse-scale 3D pores. The macropores are made by Fe3O4, which facilitate to produce meso and micro pores on their walls by KOH activation. The sample prepared at 700 °C (NSC-700) is found to have the largest specific surface area (1199 cm2 g−1) and specific capacity (241 F g−1 at current density of 1 A g−1). Its capacity is 260% as high as that of lignin amine carbon (LAC) prepared without adding Fe3O4. Excellent rate performance is unraveled because of possessing 82% specific capacity at 20 A g−1 and 27.2 Wh kg−1 energy density at 10000 W kg−1 power density. Moreover, the specific capacity maintains 95.0% after 3000 cycles, indicating good electrochemical stability. The good electrical performance of NSC-700 is attributed to its interesting electronic properties that are induced by special pore structure. Because of having merits such as high rate performance, long life, large specific capacity and low cost, our NSC is anticipated to be a promising capacitor as electrode material.

Glucose dehydrogenase (GDH) is a general tool for driving nicotinamide (NAD(P)H) regeneration in synthetic biochemistry. An increasing number of synthetic bioreactions are carried out in media containing high amounts of organic cosolvents or hydrophobic substrates/products, which often denature native enzymes, including those for cofactor regeneration. In this work, we attempted to improve the chemical stability of Bacillus megaterium GDH (BmGDHM0 ) in the presence of large amounts of 1-phenylethanol by directed evolution. Among the resulting mutants, BmGDHM6 (Q252L/E170K/S100P/K166R/V72I/K137R) exhibited a 9.2-fold increase in tolerance against 10 % (v/v) 1-phenylethanol. Moreover, BmGDHM6 was also more stable than BmGDHM0 when exposed to hydrophobic and enzyme-inactivating compounds such as acetophenone, ethyl 2-oxo-4-phenylbutyrate, and ethyl (R)-2-hydroxy-4-phenylbutyrate. Coupled with a Candida glabrata carbonyl reductase, BmGDHM6 was successfully used for the asymmetric reduction of deactivating ethyl 2-oxo-4-phenylbutyrate with total turnover number of 1800 for the nicotinamide cofactor, thus making it attractive for commercial application. Overall, the evolution of chemically robust GDH facilitates its wider use as a general tool for NAD(P)H regeneration in biocatalysis.

Objective To compare the clinical effects of body acupuncture, moxibustion, and body acupuncture plus moxibustion in the treatment of post-stroke shoulder hand syndrome (SHS). Methods A total of 90 SHS patients after stroke were randomly divided into the body acupuncture group, the moxibustion group, and the body acupuncture plus moxibustion group, with 30 cases in each. On the basis of rehabilitation and routine treatment, the patients in different groups were treated with body acupuncture, moxibustion, and body acupuncture plus moxibustion respectively. Treatment was given once a day, 5 times a week, and 4 weeks in all. The visual analogue scale (VAS) scores, edema grading scores, and simplified Fugl-Meyer assessment (FMA) scores were evaluated before and after treatment, and the therapeutic effects of patients were evaluated as well. Results After treatment, the VAS and edema grading scores of the three groups were all lower and the FMA scores were all higher than those before treatment, with statistically significant differences (all P Conclusion Body acupuncture, moxibustion, and body acupuncture plus moxibustion are all effective for post-stroke SHS, while the effect of acupuncture plus moxibustion is the best in relieving the pain and swelling, and improving effectively the joint movement of post-stroke SHS patients, which should be popularized in clinical practice.

To observe the effect of moxibustion at Feishu (BL 13) on related inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid of asthma model rats, and to explore the mechanism of moxibustion in treating asthma. A total of 48 Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a moxibustion group and a medication group, with 12 rats in each group. Except for the normal group, the rats in the other three groups were subjected to ovalbumin sensitization to stimulate the asthma. At the same time, rats in the moxibustion group received moxibustion at bilateral Feishu (BL 13), and rats in the medication group received dexamethasone by intragastric administration. Rats in the normal and the model groups only received the same fixation and normal saline by intragastric administration. After the interventions, the inspiratory resistance, the expiratory resistance, and the pulmonary compliance were measured for rats in each group; the numbers of the inflammatory cells in the bronchoalveolar lavage fluid were counted; the levels of the involved inflammatory factors in bronchoalveolar lavage fluid were detected; the pathological morphologies of the lung tissues were observed under light microscope. After modeling, compared with the normal group, the rats in the model group showed obvious asthma attack-like response, significantly increased inspiratory resistance and expiratory resistance (both P 0.05). Both moxibustion at Feishu (BL 13) and intragastric administration of dexamethasone can improve the asthma attack-like symptoms of ovalbumin-sensitized rats; regulating the inflammatory cell numbers and the inflammatory factor contents in the lung may be one mechanism of moxibustion in treating asthma.

With the reported CO2 activation for the oxidation of benzene to phenol (-ENE → -OL) by the graphitic carbon nitride g-C3N4 (CN) via an artificial photosynthetic route as inspiration, high-valent a...