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Studying the deep learning-based molecular representation has great significance on predicting molecular property, promoted the development of drug screening and new drug discovery, and improving human well-being for avoiding illnesses. It is essential to learn the characterization of drug for various downstream tasks, such as molecular property prediction. In particular, the 3D structure features of molecules play an important role in biochemical function and activity prediction. The 3D characteristics of molecules largely determine the properties of the drug and the binding characteristics of the target. However, most current methods merely rely on 1D or 2D properties while ignoring the 3D topological structure, thereby degrading the performance of molecular inferring. In this paper, we propose 3DMol-Net to enhance the molecular representation, considering both the topology and rotation invariance (RI) of the 3D molecular structure. Specifically, we construct a molecular graph with soft relations related to the spatial arrangement of the 3D coordinates to learn 3D topology of arbitrary graph structure and employ an adaptive graph convolutional network to predict molecular properties and biochemical activities. Comparing with current graph-based methods, 3DMol-Net demonstrates superior performance in terms of both regression and classification tasks. Further verification of RI and visualization also show better robustness and representation capacity of our model.

Seven photoaffinity-based and sixteen biotin-based berberine (BBR) probes were constructed and screened for their effects on c-Jun N-terminal protein kinases (JNK) phosphorylation (p-JNK) suppressi...

Isothermal oxidation behaviors of Ni–Fe (wt.%) and of the same alloy with additions of 10 and 15%Cr alloys in the air at 800 °C and 900 °C and their anodic behaviors in aluminum electrolysis system at 800 °C were evaluated. The composition morphologies of oxide scales were characterized by XRD, SEM, and EDS. Results show that the scales formed on Ni–Fe alloy at both temperatures consisted of an inner (Ni,Fe)3O4 layer and an outer Fe2O3 layer. For Ni–Fe–10Cr alloy, an external (Ni,Fe)3O4/Fe2O3 layers and an internal oxidation zone were formed at 800 °C, while a continuous Cr2O3 layer forms at the internal oxidation zone/substrate interface at 900 °C. A multilayer structure oxide of Cr2O3/(Ni,Fe,Cr)3O4/(Ni,Fe)3O4/Fe2O3 was formed on Ni–Fe–15Cr alloy at 800 °C, while at 900 °C the Fe2O3 becomes discontinuous disperses in the (Ni,Fe)3O4 layer close to the surface. Increases in oxidation temperature or Cr content for Ni–Fe–Cr alloys promote the growth of the inner Cr2O3 layer and simultaneously reduce Fe2O3 content. After 4 h of electrolysis at an anode current density of 0.25 A cm−2, the oxidation resistance of Ni–Fe–15Cr anode is superior to the Ni–Fe anode.

Molybdenum disulfide (MoS2), a typical two-dimensional transition metallic layered material, attracts tremendous attentions in the electrochemical energy storage due to its excellent physicochemical properties. However, with the deepening of the research and exploration of the lithium storage mechanism of these advanced MoS2-based anode materials, the complex reaction process influenced by internal and external factors hinders the exhaustive understanding of the lithium storage process. To design stable anode material with high performance, it is urgent to review the mechanisms of reported anode materials and summarize the related factors that influence the reaction processes. This review aims to dissect all possible side reactions during charging and discharging process, uncover internal and external factors inducing various anode reactions and finally put forward strategies of controlling high cycling capacity and super-stable lithium storage capability of MoS2. This review will be helpful to the design of MoS2-based lithium-ion batteries (LIBs) with excellent cycle performance to enlarge the application fields of these advanced electrochemical energy storage devices.

A mild and efficient photochemical multi-component tandem reaction of quinoxalin-2(1H)-ones, alkenes and sulfinic acids is reported. This tandem reaction could be conveniently carried out at room temperature by employing 4CzIPN as the metal-free photocatalyst and dioxygen (air) as the environmentally benign oxidant. A number of sulfonated quinoxalin-2(1H)-ones were obtained in satisfactory yields with favorable functional group tolerance. Radical trapping experiment and fluorescence quenching experiments were performed to elucidate this visible-light mediated radical reaction process.

The development of a scalable strategy to prepare highly efficient and stable bifunctional electrocatalysts is the key to industrial electrocatalytic water splitting cycles to produce clean hydrogen. Here, a simple and quick one-step hydrothermal method was used to successfully fabricate a three-dimensional core chrysanthemum-like FeS/Ni3S2 heterogeneous nanoarray (FeS/Ni3S2@NF) on a porous nickel foam skeleton. Compared with the monomer Ni3S2@NF, the chrysanthemum-like FeS/ Ni3S2@NF heterostructure nanomaterials have improved catalytic performance in alkaline media, showing low overpotentials of 192 mV (η10) and 130 mV (η-10) for OER and HER, respectively. This study attests that integrated interface engineering and precise morphology control are effective strategies for activating the Ni3+/Ni2+ coupling, promoting charge transfer and improving the intrinsic activity of the material to accelerate the OER reaction kinetics and promote the overall water splitting performance. The scheme can be reasonably applied to the design and development of transition metal sulfide-based electrocatalysts to put into industrial practice of electrochemical water oxidation.

An efficient construction of oxazoline-containing polycyclic scaffolds is presented through a Pd-catalyzed addition/cyclization of (hetero)arenes tethered O-acyl cyanohydrin units and arylboronic acids. A diversity of oxazoline-containing polycyclic compounds can be prepared in good to high yields under the mild reaction conditions. This method can be extended to prepare multi-substituted polycyclic heterocyclic compounds via a Pd-catalyzed addition/cyclization/arylation tandem sequence by using arylboronic acid and different heteroarene scaffolds such thiophene, pyrrole and furan analogues.

This review highlights the biological importance of mitochondrial energy metabolism and the applications of multiple optical/electrochemical approaches to determine energy metabolites. Mitochondria, the main sites of oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis, provide the majority of energy required by aerobic cells for maintaining their physiological activity. They also participate in cell growth, differentiation, information transmission, and apoptosis. Multiple mitochondrial diseases, caused by internal or external factors, including oxidative stress, intense fluctuations of the ionic concentration, abnormal oxidative phosphorylation, changes in electron transport chain complex enzymes and mutations in mitochondrial DNA, can occur during mitochondrial energy metabolism. Therefore, developing accurate, sensitive, and specific methods for the in vivo and in vitro detection of mitochondrial energy metabolites is of great importance. In this review, we summarise the mitochondrial structure, functions, and crucial energy metabolic signalling pathways. The mechanism and applications of different optical/electrochemical methods are thoroughly reviewed. Finally, future research directions and challenges are proposed.

Medium-chain triglyceride (MCT) and eicosapentaenoic acid (EPA) has been widely applied in nutritional supplementation. However, when administered individually or mixed, they were unable to maximize their nutritional value. Hence, EPA-rich medium- and long-chain triacylglycerol (MLCT) was synthesized from MCT and EPA-rich fish oil (FO) by enzymatic transesterification. The fatty acids in triglyceride (TAG) were rearranged and resulted in significant changes in TAG profiles compared to physical mixture of MCT and FO (PM). EPA-containing MML (MML, MLM and LMM) and LLM (LLM, LML and MLL) type TAGs account for 70.21%. The fate of different oils (MCT, FO, PM, and MLCT) across the gastro-intestinal tract was subsequently simulated by an in vitro digestion model. The results showed that the physical and structural characteristics of different oils during digestion depended upon the oil type and the microenvironment they were in. The degree of hydrolysis for MLCT was higher than that for the other three oils. FFAs release level was presented in the following order: MLCT＞MCT＞PM＞FO. This can be attributed to the composition and positional distribution of fatty acids in TAGs. What is more, LCFAs (EPA) in MLCT mainly existed in the form of sn-2 MAG, which was conducive to their subsequent absorption and transport.These results may aid in the future rational design of structural lipids, thereby regulating lipid digestion and maximizing the nutritional value of oils.

Objective To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa. Methods The crude polysaccharide from roots of B. rapa (BRP) was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis. Results Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity, including increasing production of nitric oxide (NO), tumor necrosis factor α (TNFα) and upregulating mRNA levels of inducible NO synthase (iNOS) and TNFα. Furthermore, modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B (NF-κB). Conclusion The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel ester derivative of paeoniflorin, which has been shown to have synergistic pharmacodynamic effects with leflunomide (LEF). To determine the effects of CP-25 on the pharmacokinetics of LEF in rats, we developed an UPLC-MS/MS-based method for the determination of levels of teriflunomide (TER, an active metabolite of LEF). This method was used to determine TER concentrations in the plasma, urine, feces, and bile, heart, liver, spleen, lung, kidney, intestinal, brain, and synovial tissues, and peripheral blood mononuclear cells (PBMCs) of rats in the control [LEF (10 mg/kg)] and combined [CP-25(50 mg/kg×7d) plus LEF (10 mg/kg)] groups. TER AUC, Tmax , MRT, t1/2α , and t1/2β were significantly lower and CL was significantly higher in the combined group than in the control group. Oral CP-25 administration in combination with LEF was found to promote TER excretion in urine, feces, and bile, and to reduce its contents in most tissues and organs, especially in the liver, which may reduce LEF-induced liver injury. CP-25 also increased TER exposure in the synovium and its absorption by PBMCs, and this could explain the synergistic effects of CP-25 and LEF.

Ammonia plays an important role in production and life, but the high energy consumption of the industrial Haber–Bosch process encourages people to study nitrogenase, which can convert nitrogen into...

Ceramic/resin composite is an important thermal management material for electronic packaging. The formation of a thermally conductive network of ceramic fillers in the composite is the key to improving thermal conduction performance. We design a method of ice-templated self-assembly followed by hot pressing to prepare oriented boron nitride/polyvinyl alcohol (BN/PVA) composites. First, the BN/PVA aerogel is made by freezing and then freeze-drying. BN flakes are squeezed by ice crystals to form a 3D network at the ice interfaces. After further removing the gaps between the BN flakes by hot pressing, a dense BN/PVA composite material is obtained. The resulting polymer composite has a thermal conductivity up to 10.04 W m−1 K−1 at h-BN content of 68 wt%. Theoretical analysis shows a low interfacial thermal resistance between BN flakes. This approach can potentially be used in advanced electronic packaging technology, especially in the design of thermal interface materials.

Bacteria survived and thrived inside any part of plant without damaging its host are called endophytic bacteria. Many studies have focused on plant–endophytic bacterium interactions and their Plant-growth-promoting (PGP) abilities. Albino tea plants are widely investigated because of their high amino acid concentrations. Previous studies mainly elucidated specific metabolite mechanisms in albino tea plants, while the present study identified the variation in diversity and endophytic bacterial abundance in albino and non-albino tea leaves using culture-dependent and culture-independent methods. With different culture media, we identified a total of 110 isolates, of which 58 endophytic bacteria belonged to three phyla (Proteobacteria, Firmicutes, and Actinobacteria). Moreover, we identified a total of 1856 operational taxonomic units as 513 endophytic bacteria belonging to 27 phyla including Proteobacteria, Firmicutes, and Actinobacteria. In addition, comparing to non-albino tea leaves, endophytic bacteria obtained from albino tea leaves showed higher diversity and abundance. Endophytic bacteria isolated from albino leaves also exhibited higher PGP properties than those from non-albino ones, and their PGP effects on rice and tea cuttings were examined. The results indicated differences in endophytic bacteria between albino and non-albino leaves. Specific endophytic bacteria isolated from albino leaves may have a relationship with the albino phenotype. Our study indicated that PGP bacteria isolated from albino leaves are expected to become a plant growth promoter in the future.

A kind of anion exchange membranes (AEMs) with C C bond end-group crosslinked structure was synthesized successfully. Unlike the traditional aliphatic AEMs, the AEMs were prepared in this work by a strategy to realize the C C bond thermal end-group crosslinking reaction, exhibiting an obvious microphase separation structure and a suitable dimensional stability. The well-defined ion channels constructed in the AEMs guarantee the fast OH− conduction, as confirmed via physical and chemical characterization. The conductivity was dramatically enhanced due to the effective ion channels and increased ion exchange capacity. Among the as-prepared AEMs, the PHFB-VBC-DQ-80% AEM has a conductivity of 135.80 mS cm−1 at 80 °C. The single cell based on PHFB-VBC-DQ-80% can achieve a power density of 141.7 mW cm−2 at a current density of 260 mA cm−2 at 80 °C. The AEMs show good thermal stability verified by a thermogravimetric analyzer (TGA). Furthermore, the ionic conductivity of PHFB-VBC-DQ-80% only decreased by 7.1% after being soaked in a 2 M NaOH solution at 80 °C for 500 h.

Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90- to 450-fold and 5- to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.

In this study, four kinds of In2O3 photocatalysts were prepared by a facile calcination process at different temperatures and used for the removal of perfluorooctanoic acid (PFOA) from contaminated...

Oritavancin is a new-generation semisynthetic lipoglycopeptide antibiotic used to prevent the spread of vancomycin-resistant Gram-positive bacteria. The glycopeptide A82846B is the direct precursor of oritavancin. Considering the structural similarity between A82846B and vancomycin, the vancomycin producer Amycolatopsis orientalis was used as a chassis for the construction of a strain producing high-quality A82846B. To construct the A82846B synthetic pathway, we established a highly efficient CRISPR-Cas12a system by optimizing the conditions of conjugation and by screening the regulatory elements in the A. orientalis, which is difficult to be genetically manipulated. The efficiency of gene knockout was almost 100%. The glycosyltransferases module (gtfDE) and glycosyl synthesis module (vcaAEBD) in the vancomycin gene cluster were replaced with the corresponding glycosyltransferases module (gtfABC) and glycosyl synthesis module (evaAEBD) in the A82846B cluster, respectively. A82846B was successfully produced by the artificially constructed synthetic pathway. Moreover, the titer of A82846B was increased 80% by expressing the pathway-specific regulatory strR. This strategy has excellent potential for remodification of natural products to solve antibiotic resistance.

Emerging evidence has shown that endoplasmic reticulum (ER) stress promotes sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanisms are poorly understood. The purpose of this study was to explore the mechanism by which ER stress promotes sorafenib resistance in HCC. We found that pyruvate kinase isoform M2 (PKM2) was highly expressed in human HCC tissues and co-related with worse clinicopathologic features and overall survival. Activation of ER stress positively correlated with PKM2 expression both in HCC tissue samples and tunicamycin (TM)-induced HCC cell lines. PKM2 knockdown increased sorafenib-induced apoptosis and decreased the ability of colony formation, while upregulation of PKM2 reverses this phenomenon. Furthermore, high-throughput sequencing identified that activation of ER stress significantly downregulated the expression of miR-188-5p in HCC cells. According to bioinformatics analysis and dual-luciferase assays, we further confirmed that hnRNPA2B1 is the target gene of miR-188-5p. Downregulating the expression of hnRNPA2B1 with siRNA could decrease the expression of PKM2 and enhance sorafenib-induced apoptosis in HepG2 cells. Our study demonstrated that ER stress could promote sorafenib resistance through upregulating PKM2 via miR-188-5p/hnRNPA2B1. Therefore, targeting the miR-188-5p/hnRNPA2B1/PKM2 pathway and ER stress may prove instrumental in overcoming sorafenib resistance in HCC treatment., Graphical abstract, The underlying mechanisms of endoplasmic reticulum (ER) stress that promote sorafenib resistance in hepatocellular carcinoma (HCC) are poorly understood. This study demonstrated that ER stress could promote sorafenib resistance by upregulating PKM2 via miR-188-5p/hnRNPA2B1. Therefore, targeting the miR-188-5p/hnRNPA2B1/PKM2 pathway and ER stress may prove instrumental in overcoming sorafenib resistance in HCC treatment.

The involvement of Dexmedetomidine (Dex) has been indicated in postoperative cognitive dysfunction (POCD), while the mechanism is not well characterized. This study estimated the mechanism of Dex in POCD. Rats were anesthetized with sevoflurane (SEV) to evoke POCD and then subjected to Morris water maze test to detect the cognitive and behavioral function. Then, the damage of hippocampus and cortex, and apoptosis and activity of neurons were examined. Microarray analysis was performed to screen out the differentially expressed microRNAs (miRs) in rats after Dex treatment. The cognitive and behavioral functions and neuronal activity of rats were detected after miR-129 antagomir injection. The target of miR-129 was predicted. The levels of TLR4 and NF-κB p65 in hippocampus and cortex were measured. Dex treatment alleviated SEV-induced behavior and cognitive impairments in rats, promoted neuronal activity and hindered neuronal apoptosis. After treatment with Dex, miR-129 expression was elevated in brain tissues, and the neuroprotection of Dex on POCD rats was partially annulled after injection of miR-129 antagomir. Furthermore, miR-129 targeted TLR4 and prevented the phosphorylation of NF-κB p65. In summary, Dex ameliorated SEV-induced POCD by elevating miR-129 and inhibiting TLR4 and NF-κB p65 phosphorylation. This study may shed new lights on POCD treatment.

A green heterogeneous acid catalyst derived from agro-industrial waste obtained from ginger straw was prepared via partial carbonization, followed by sulfonation using sulfuric acid. Three variables, including the carbonization temperature, carbonization time and sulfonation temperature, were optimized to achieve the ideal preparation conditions and the as-synthesized catalyst was characterized using X-ray diffraction, elemental analysis, scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, Raman spectroscopy, N2 adsorption-desorption and acid density studies to reveal the relationship between its catalytic performance and physical-chemical properties. The results show that the ginger straw-based catalyst prepared via carbonization for 60 min at 350 °C, followed by sulfonation at 105 °C, has an amorphous carbon structure with an –SO3H group density of 1.05 mmol/g. In addition, the catalyst exhibits thermal stability up to 200 °C and satisfactory catalytic performance (93.2% conversion) during the esterification of oleic acid using methanol under the optimized reaction conditions (9:1 M ratio of methanol to oleic acid; catalyst loading, 7 wt%; reaction temperature, 64 °C; reaction time, 210 min). Although its catalytic activity was later found to decrease with cycling, the spent catalyst remains stable after the 5th cycle with a conversion of 65.6%.

Uracil DNA glycosylase (UDG) is one of the key initiators for the base excision repair pathway. Since abnormal UDG expression is associated with various diseases, sensitive detection of UDG activity is critical for early clinical diagnosis. Here, a smart catalyzed hairpin assembly (CHA)-DNAzyme nanosystem is developed for intracellular UDG imaging by incorporating CHA and DNAzyme onto MnO2 nanosheets. In this strategy, the biodegradable MnO2 nanosheets are employed as nanocarriers for efficiently adsorbing and delivering five DNA probes into cells by endocytosis. Then, the MnO2 nanosheets are degraded by cellular glutathione to release the DNA modules at the same intracellular position. Liberated Mn2+, an indispensable DNAzyme cofactor, was used to promote catalytic cleavage for facilitating the cascade process in cells. Based on the uracil site-recognition and -excision operation of the target UDG, the activated CHA-DNAzyme nanosystem generates lots of DNAzyme-assisted CHA products, turning on the fluorescence resonance energy transfer response. This autocatalytic CHA-DNAzyme nanosystem provides a detectable minimum UDG concentration of 0.23 mU/mL, which is comparable to some reported UDG detection approaches. As a multiple signal amplification strategy, the CHA-DNAzyme nanosystem realizes the UDG imaging in living cells with enhanced sensitivity, indicating great promise in the prediction and diagnosis of early-stage cancer.

Tryptophan 2,3-dioxygenase (TDO2) was an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. We undertook this study to determine a comprehensive analysis of TDO2 expression in immune cells and assess the characterization of immune cell phenotype in TDO2 knockout mice. The expression of TDO2 in various tissues of DBA/1 mice was detected by quantitative real-time PCR (qPCR) and immunohistochemistry. Both flow cytometry and immunofluorescence were used to analyze the expression of TDO2 in immune cells. Furthermore, TDO2 knockout (KO) mice were generated by CRISPR/Cas9 technology to detect immune cell phenotype. TDO2 protein level in liver was tested by western blot. High-performance liquid chromatography was used to detect the level of Trp and Kyn. Flow cytometry was used to test the proportions of splenic lymphocyte subsets in wild-type (WT) and TDO2 KO mice. We found that TDO2 was expressed in various tissues and immune cells, and TDO2 staining was mainly observed in the cytoplasm of cells. There was no difference in the development of immune cells between TDO2 KO mice and WT mice, including T cells, B cells, memory B cells, plasma cells, dendritic cells, and natural killer cells. Interestingly, the reduced M1/M2 ratio was observed in the peritoneal macrophages of TDO2 KO mice. Taken together, these findings enriched the known expression profile of TDO2, especially its expression in immune cells. Our study suggested that TDO2-mediated Trp-Kyn metabolism pathway might be involved in the immune response.

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng-Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1 ), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all-cause (HR (95% CI) = 1.12 (1.10-1.14) and 1.08 (1.07-1.10), respectively) and cause-specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1-point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7-9 h/night) was associated with a 0.21-year decrease in the AgingAccel (95% CI: -0.27 to -0.15) and a 0.4% decrease in the aging rate (95% CI: -0.5% to -0.3%). This study developed a machine learning-based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.

CeO2/g-C3N4 heterojunction photocatalyst had been successfully fabricated through a one-step in-situ pyrolysis formation of 3D hollow CeO2 mesoporous nanospheres and 2D g-C3N4 nanosheets together with simultaneous removal of carbon sphere templates after heat treatment. The sample shows high catalytic performances for photocatalytic hydrogen generation and photocatalytic oxidation of Bisphenol A (BPA) under visible light irradiation, and the catalytic degradation route of BPA was suggested by the degradation products determined by GC–MS. The enhancing catalytic activity was attributed to the effective interfacial charge migration and separation. Finally, it was proposed that the CeO2/g-C3N4 heterojunction photocatalyst could follow a more appropriate Z-scheme charge transfer mechanism, which was confirmed by the analysis of experiment and theoretical calculation results.

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins’ interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients’ prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients’ prognosis and provide meaningful guidance for clinical treatment.

The dissociation of H2O is a crucial aspect for the water-gas shift reaction, which often occurs on the vacancies of a reducible oxide support. However, the vacancies sometimes run off, thus inhibiting H2O dissociation. After high-temperature treatment, the ceria supports were lacking vacancies because of sintering. Unexpectedly, the in situ generation of surface oxygen vacancies was observed, ensuring the efficient dissociation of H2O. Due to the surface reconstruction of ceria nanorods, the copper species sustained were highly dispersed on the sintered support, on which CO was adsorbed efficiently to react with hydroxyls from H2O dissociation. In contrast, no surface reconstruction occurred in ceria nanoparticles, leading to the sintering of copper species. The sintered copper species were averse to adsorb CO, so the copper-ceria nanoparticle catalyst had poor reactivity even when surface oxygen vacancies could be generated in situ.

Aortic regurgitation (AR) is a volume overload disease causing eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis is involved in many cardiovascular diseases, but whether they also participate in AR-induced heart failure is still elusive. In this study, we found ER stress activation in myocardial samples from patients with AR. With a unique murine model of AR which induced eccentric cardiac hypertrophy and heart failure, we also found aggravation of cardiac ER stress and apoptosis, as evidenced by a reduction of Bcl-2/Bax ratio and an increase of caspase-3 cleavage. We then examined the signaling effectors involved in ER-initiated apoptosis and found volume overload specifically activated C/EBP homologous protein (CHOP), but not caspase-12 or Jun N-terminal kinase (JNK). Interestingly, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, improved cardiac function, and suppressed ER stress, apoptosis, and CHOP. Furthermore, genetic knockdown of CHOP inhibited cardiac Bcl-2/Bax ratio reduction and caspase-3 activation and rescued cardiac dysfunction. In summary, our findings suggest that ER stress-CHOP signaling is involved in the development of volume overload cardiac hypertrophy induced by AR through promoting cardiomyocytes apoptosis and provide a previously unrecognized target in heart failure induced by volume overload.

Transition-metal-catalyzed C–H bond addition to nitriles has emerged as a powerful synthetic approach for the construction of C–C bonds in organic synthesis. Due to the merits of atom- and step-economy, as well the easy availability of the starting materials, these transformations not only deliver acyclic aryl ketone products with nitriles­ as C-building blocks, but can also be utilized for the highly efficient­ assembly of azaheterocyclic skeletons using nitriles as C–N building blocks. This short review summarizes recent progress on transition-metal-catalyzed C–C bond-forming reactions based on C(sp2)–H and C(sp3)–H additions to nitriles.1 Introduction2 Palladium-Catalyzed C–H Addition to Nitriles2.1 Palladium-Catalyzed C–H Addition to Nitriles for the Preparation of Ketone (Imine) Products2.2 Palladium-Catalyzed C–H Addition to Nitriles for the Preparation of Azaheterocycles2.3 Palladium-Catalyzed C–H Addition to Nitriles/1,2-Rearangement3 Other Transition-Metal-Catalyzed C–H Additions to Nitriles4 Summary and Outlook

The extrusion-casting process can realize large-area and continuous preparation of polymer-based films. In this paper, five different types of polyvinylidene fluoride (PVDF)-based piezoelectric films: PVDF, PVDF/PZT, PVDF/PZT@105, PVDF/PZT/BNNS and PVDF/PZT@105/BNNS were prepared by the extrusion-casting process. The mechanical, dielectric, thermal conductivity and piezoelectric properties were studied. It is found that PZT particles can well improve the dielectric performance and also the mechanical stability under variable temperature conditions. PZT powders modified by titanate coupling reagent (UP-105) can further improve the performance of the PVDF/PZT@105 films by improving the combination and dispersion of organic and inorganic phases. The addition of boron nitride nanosheets (BNNS) can improve the thermal conductivity of the films and the breakdown strength. The piezoelectric coefficient (d33) of PVDF/PZT@105/BNNS composite film can reach 21pC/N, compared with the neat PVDF film (4pC/N) and PZT/PVDF (9pC/N) film realizing great improvement.

Water contamination by mercury ions (Hg2+) causes irreversible and serious effect on the ambient environment, ecological systems, and human health, necessitating further improvement of Hg2+ monitoring at low concentrations. Here, we proposed a novel surface plasmon resonance (SPR) sensor for Hg2+ detection with desirable advantages of high sensitivity, simple operation, label-free, and low cost, in which the chitosan/poly (vinyl alcohol)/SnO2 composite film was modified on sensing surface as the active layer for sensitivity enhancement. Benefiting from the relatively high refractive index of SnO2 nanoparticles, the evanescent field generated at the metal-solution interface can be significantly enhanced, which results in a 5 times improvement of sensitivity. Through appropriate optimization in the aspects of componential constitutions, the sensor exhibits excellent sensitivity of 25.713 nm/μg/L and ultra-low calculated detection limit of 6.61 ng/L(32.95 pM). Such detection limit is strikingly lower than the limitation (10 nM) in drinking water set by the US Environmental Protection Agency. In addition, the as-prepared sensor presents relatively high selectivity for Hg2+, attributing to plenty of binding sites for specific adsorption produced by functionalized chitosan/poly (vinyl alcohol) composites, which have been furtherly verified by characterization of FTIR and XPS spectra. The proposed sensor also exhibits great repeatability and good time stability for 15 days. This work provides a promising strategy for developing high-performance SPR sensor for Hg2+ detection and a prospective application in environmental monitoring.

Background: This study aimed to investigate the expression of regeneration-related genes in canine urine during bladder repair. Materials & methods: Canine urine samples were collected after partial cystectomy. Regenerative mRNA of hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), key stem cell transcription factors and cholinergic signals were detected. Results: HIF-1α, VEGF, CD44, IL-6 and prominin-1 expression in canine urine after partial cystectomy exhibited two similar peaks at ∼2 weeks. HIF-1α and VEGF expression were higher in the afternoon than the morning. The expression of key stem cell transcription factors and cholinergic signals also exhibited a rhythm along with bladder healing. Conclusions: The expression of HIF-1α, VEGF, key stem cell transcription factors and cholinergic signals exhibited a time curve distribution during canine bladder healing. The expression trend of some regenerative genes was similar during bladder healing, and a cooperative effect may exist.

Electrocatalytic reduction of CO2 is one of the most attractive approaches for converting CO2 into valuable chemical feedstocks and fuels. This work reports a catalyst comprising graphdiyne-decorated bismuth subcarbonate (denoted as BOC@GDY) for efficient electroreduction of CO2 to formate. The BOC@GDY shows a stable current density of 200 mA cm−2 at –1.1 V in a flow cell configuration, with a faradaic efficiency of 93.5% for formate. Experimental results show that the synergistic effect in BOC@GDY is beneficial for the CO2 adsorption affinity, the reaction kinetics and the selectivity for formate. In addition, in-situ X-ray absorption and Raman spectroscopy indicate that the electron-rich GDY could facilitate the reduction from Bi(III) to Bi(0), thus leading to more active sites. We also demonstrate that the promoting effect of GDY in CO2 electroreduction can be further extended to other metal catalysts. To the best of our knowledge, such general promoting functions of GDY for CO2 electroreduction have not been documented thus far.

Non-bovine milk is an underappreciated type of milk with geographical characteristics of production, consumption and nutrition. Although the structure similarity of microbial community from the different types of non-bovine milk are very different, the composition of microbial community, especially those belonging to pathogenic bacteria or lactic acid bacteria in non-bovine milk, may be more diverse than that of cow milk. Microbial community analysis based on high-throughput sequencing coupled with microbial annotation on species level, environmental factors of milk producing areas, and milk nutritional composition is considered to be very necessary strategy in future research of non-bovine milk. This review provides a reference for evaluating food safety and nutrition of non-bovine milk and dairy products.

The rhamnogalacturonan acetylesterase gene (named pp1113), encoding a novel cold-adapted rhamnogalacturonan acetylesterase, was cloned from Paenibacillus polymyxa. pp1113 was functionally expressed in Escherichia coli by inducing expression at 20 °C for 16 h. The pH and temperature optimums for the recombinant enzyme were 8.5 and 30 °C, respectively. As an SGNH-type acetylesterase, pp1113 demonstrated high activity against acetyl ester substrates and could maintain approximately 60 % activity at 0 °C.The specific activity of purified pp1113 was 65.95 U/mg (C2). The Km and Vmax values of purified pp1113 were 3.89 mM and 81.07 μmol/min, respectively. We obtained an R232L variant with improved thermal stability and catalytic activity through site-directed mutagenesis. T1/2 of R232L at 50 °C increased from less than 30 min to 6 h when compared to wild-type pp1113, and T1/2 extended to 8 h after immobilization. The R232L mutant improved the conversion rate of 0.1 M cinnamyl alcohol at 40 °C to 94 % in the reaction of synthesis of cinnamyl acetate. After purification, the R232L mutant was immobilized (pH 8.0 phosphate buffer 0.5 M, 20 h at 20 °C, protein loading reached 17 mg/g). This was the first report of the rhamnogalacturonan acetylesterase gene obtained from Paenibacillus polymyxa with detailed enzymatic properties.

Background Epileptic seizure is a process of energy accumulation, bursting, and depletion accompanied by the production, spread, and termination of epileptic discharges. The energy required for a seizure is mainly provided through mitochondrial production of ATP. Mitochondrial diseases often lead to epileptic seizures, and energy depletion caused by seizures can lead to mitochondrial dysfunction. The energy metabolism has become a key target for treatment of epileptic diseases. Method The effect of OSI-906, an insulin receptor (IR)/ insulin-like growth factor 1 receptor (IGF-1R) inhibitor, on behaviors and electroencephalographic activity in the lithium-pilocarpine rats were tested. 18F-FDG positron emission tomography (PET)/ computed tomography (CT) was performed to detect the relative whole-brain glucose uptake values. Electron microscopy was performed to observe the ultrastructure of neuronal and mitochondrial damage. The changes in blood glucose at different time points before and after the intervention were tested and the effects of OSI-906 on IR/IGF-1R and downstream Akt signaling in the context of seizures were evaluated. Results The OSI-906 treatment applied 3 days before the pilocarpine-induced seizures significantly reduced the seizure severity, prolonged the seizure latency and decreased the EEG energy density. MicroPET/CT revealed that 50 mg/kg of OSI-906 inhibited the 18F-FDG glucose uptake after epileptic seizures, suggesting that OSI-906, through inhibiting IR/IGF-1R and the downstream AKT signaling, may regulate the excessive energy consumption of the epileptic brain. The OSI-906 treatment also reduced the mitochondrial damage caused by epileptic seizures. Conclusion The IR/IGF-1R inhibitor OSI-906 can significantly reduce the sensitivity and severity of pilocarpine-induced seizures by inhibiting the IR/IGF-1R and the downstream Akt signaling pathway.

Two novel 3-D Ln(III)–Cu(I) heterometallic coordination polymers, [Ln2Cu2(L3)4(C2O4)2]·H2O (Ln = Sm, Eu; HL3 = 5-aminonicotinic acid), were hydrothermally produced by reacting lanthanide oxide and copper halide with 5-aminonicotinic acid and orotic acid. In the two isostructural complexes, {Ln6}-wheel clusters link each other via edge-sharing mode, constructing honeycomb-like layers which stack in –ABAB– mode. On the whole, the architectures can be described as sandwich framework constructed by {Ln6}-wheel layers pillared by interlamellar [CuOL32] triangle pillars. The electronic structure was theoretically calculated by the density functional theory, confirming the direct transition character. The steady and transient photoluminescent spectra were measured, from which the intensity parameters, radiative lifetime and quantum efficiency were calculated within the framework of the Judd–Ofelt theory. [Eu2Cu2(L3)4(C2O4)2]·H2O can be regarded as a potential candidate for LED applications.

The changes of fibroblast-like synoviocytes (FLSs) and vascular endothelial cells (VECs) biological functions are closely related to angiogenesis in rheumatoid arthritis (RA). Nevertheless, how the crosstalk between FLSs and VECs interferes with RA is far from being clarified. Herein, we studied the effect of the reciprocal interactions between FLSs and VECs on angiogenesis and mechanism of geniposide (GE). After administration of GE, improvement of synovial hyperplasia in adjuvant arthritis rats was accompanied by downregulation of SphK1 and p-Erk1/2. The dynamic interaction between FLSs and VECs triggers the release of S1P by activating p-Erk1/2 and SphK1, then activating RhoA-F-actin and Ras-Erk1/2 pathways. When exposed to the inflammatory microenvironment mediated by FLSs-VECs crosstalk, proliferation, migration, and permeability of VECs were enhanced, the angiogenic factors were imbalanced. Meanwhile, the proliferation and secretory ability of FLSs increased. Interestingly, depletion of S1P or blocking of the activation of SphK1 by GE and PF-543 prevented the changes. In conclusion, S1P released during FLSs-VECs crosstalk changed their biological functions by activating RhoA-F-actin and Ras-Erk1/2 pathways. GE acted on p-Erk1/2 and SphK1, inhibited the secretion of S1P, and blocked the interplay between FLSs and VECs. These results provide new insights into the mechanism of angiogenesis in RA.

Choroidal neovascularization induced by age-related macular degeneration and retinal neovascularization induced by diabetic retinopathy-two leading causes of blindness-are often treated using antibodies targeting vascular endothelial growth factor (VEGF). Here we report a strong association between inflammation and high VEGF expression in aqueous humour samples from patients with choroidal or retinal neovascularization, and show that intravitreally injected exosomes derived from regulatory T cells and conjugated with an anti-VEGF antibody via a peptide linker that is cleavable by matrix metalloproteinases markedly suppressed ocular neovascularization in mouse and non-human primate models of choroidal neovascularization. The engineered exosomes, which selectively accumulate in the neovascularization lesions, could be adapted for other combination therapies of therapeutic antibodies and anti-inflammatory cargo.

We present a chemical approach to profile fatty acid uptake in single cells. We use azide-modified analogues to probe the fatty acid influx and surface-immobilized dendrimers with dibenzocyclooctyne (DBCO) groups for detection. A competition between the fatty acid probes and BHQ2-azide quencher molecules generates fluorescence signals in a concentration-dependent manner. By integrating this method onto a microfluidics-based multiplex protein analysis platform, we resolved the relationships between fatty acid influx, oncogenic signaling activities, and cell proliferation in single glioblastoma cells. We found that p70S6K and 4EBP1 differentially correlated with fatty acid uptake. We validated that cotargeting p70S6K and fatty acid metabolism synergistically inhibited cell proliferation. Our work provided the first example of studying fatty acid metabolism in the context of protein signaling at single-cell resolution and generated new insights into cancer biology.