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Density functional theory (DFT) was employed to explore the reaction mechanism, regio- and diastereoselectivities of nickel-initiated [3+2] cycloaddition between vinylcyclopropane (VCP) and N-tosylbenzaldimine assisted by phosphine ligands. Four different binding modes of the nickel center to VCP substrate were explored during the ring-opening of VCP, among which the C,C_anti and C,C_syn modes were verified to be the most accessible ones. Further explorations about four different phosphine ligand-assisted reactions based on the two most probable binding modes show that the difference in binding mode of bi- and monodentate phosphine ligands can vary the optimal reaction pathway, especially in the [3+2] cycloaddition process between the ring-opened intermediate and N-tosylbenzaldimine. The formation of C–C and C–N bonds between N-tosylbenzaldimine and the ring-opened intermediate through [3+2] cycloaddition is found to be stepwise, with the former acting as the rate-determining step (RDS) in most cases. Computed free energy barriers of RDS transition states on the optimal path I or II not only give out good predictions for reaction rates and half-lives, but also provide reasonable explanations for the major generation of cis-pyrrolidine. Noncovalent interaction analyses of key stationary points suggest the rate is influenced by both electronic effects and steric hindrance, while the diastereoselectivity is mainly controlled by electronic effects.

This prospective, multicentre, interventional study evaluated the efficacy of a modified treat-and-extend (mTAE) aflibercept regimen as personalized therapy for macular oedema (MO) due to central retinal vein occlusion (CRVO). Fifty eyes were studied from 50 patients who were enrolled between November 2016 and July 2019. All patients received intravitreal aflibercept (IVA) injections on an mTAE regimen for 24 months. Primary outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 12 months. Secondary endpoints were BCVA and CST at 24 months. Mean (standard deviation) baseline BCVA (logMAR) and CST were 0.50 (0.51) and 557 (240) µm, respectively. BCVA and CST showed significant improvements at month 12 (0.19 (0.38) and 275 (98) µm, respectively; both p < 0.0001, paired t-test). BCVA and CST also showed significant improvements at 24 months (0.26 (0.50) and 255 (91) µm, respectively, p = 0.0004 and p < 0.0001, paired t-test). The mean numbers of IVA injections and clinic visits over the 24-month study period were 6.2 (3.0) and 10.3 (1.0), respectively. The mTAE regimen of IVA injections for MO due to CRVO was effective in improving BCVA and decreasing CST at 24 months. The mTAE regimen might be an effective personalized therapy for CRVO.

This study aimed to evaluate the long-term (24-month) efficacy and safety of a modified treat-and-extend (mTAE) regimen of aflibercept for macular edema (ME) due to branch retinal vein occlusion (BRVO). This was a prospective multicenter intervention study. We evaluated 50 eyes in 50 patients with ME due to BRVO enrolled between October 2016 and September 2017. The patients received intravitreal aflibercept (IVA) injections according to a mTAE regimen for 24 months. This study reports the secondary endpoints of best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 24 months and compares them with previously reported primary endpoints. Compared with baseline BCVA and CST of 0.33 (0.27) and 488 (165) µm (mean (standard deviation)), respectively, BCVA and CST were significantly improved at 12 and 24 months (12 months: 0.059 (0.19) LogMAR and 299 (112) µm; 24 months: 0.034 (0.18) LogMAR and 272 (81) µm, respectively; both p < 0.0001). Over the 24-month period, the mean number of IVA injections and clinic visits was 7.4 (3.3) and 11.1 (2.0), respectively. The mTAE regimen of IVA injections for ME due to BRVO was effective for improving BCVA and reducing CST over 24 months. This regimen shows promise for reducing the number of injections and clinic visits.

Submergence impedes photosynthesis and respiration but facilitates aerenchyma formation in bermudagrass. Still, the regulatory genes underlying these physiological responses are unclear in the literature. To identify differentially expressed genes (DEGs) related to these physiological mechanisms, we studied the expression of DEGs in aboveground and underground tissues of bermudagrass after a 7 d treatment under control (CK), shallow submergence (SS), and deep submergence (DS). Results show that compared with CK, 12276 and 12559 DEGs were identified under SS and DS, respectively. Among them, the DEGs closely related to the metabolism of chlorophyll biosynthesis, light-harvesting, protein complex, and carbon fixation were down-regulated in SS and DS. Meanwhile, a large number of DEGs involved in starch and sucrose hydrolase activities, glycolysis/gluconeogenesis, tricarboxylic acid (TCA) cycle, and oxidative phosphorylation were down-regulated in aboveground tissues of bermudagrass in SS and DS. Whereas in underground tissues of bermudagrass these DEGs were all up-regulated under SS, only beta-fructofuranosidase and α-amylase related genes were up-regulated under DS. In addition, we found that DEGs associated with ethylene signaling, Ca2+-ROS signaling, and cell wall modification were also up-regulated during aerenchyma formation in underground tissues of bermudagrass under SS and DS. These results provide the basis for further exploration of the regulatory and functional genes related to the adaptability of bermudagrass to submergence.

Given the thermal management problem aroused by increasing power densities of electronic components in the system, graphene-based papers have raised considerable interest for applications as thermal interface materials (TIMs) to solve interfacial heat transfer issues. Significant research efforts have focused on enhancing the through-plane thermal conductivity of graphene paper; however, for practical thermal management applications, reducing the thermal contact resistance between graphene paper and the mating surface is also a challenge to be addressed. Here, a strategy aimed at reducing the thermal contact resistance between graphene paper and the mating surface to realize enhanced heat dissipation was demonstrated. For this, graphene paper was decorated with polydopamine EGaIn nanocapsules using a facile dip-coating process. In practical TIM application, there was a decrease in the thermal contact resistance between the TIMs and mating surface after decoration (from 46 to 15 K mm2 W−1), which enabled the decorated paper to realize a 26% enhancement of cooling efficiency compared with the case without decoration. This demonstrated that this method is a promising route to enhance the heat dissipation capacity of graphene-based TIMs for practical electronic cooling applications.

Purpose: To assess the efficacy and safety of a modified treat-and-extend (mTAE) regimen of aflibercept for macular edema (ME) due to branch retinal vein occlusion (BRVO). Methods: This prospective multicentre intervention study evaluated 50 eyes of 50 patients enrolled from October 2016 to September 2017. The patients received intravitreal aflibercept (IVA) injections on an mTAE regimen for a total of 12 months. The main outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 12 months. Results: The baseline BCVA and CST were 0.33 (0.27) and 488 (171) µm (mean (standard deviation)), respectively. The BCVA and CST were significantly improved at month 12 (0.067 (0.19) LogMAR and 295 (110) µm; both p < 0.0001, paired t-test). The mean number of clinic visits and IVA injections was 6.71 (1.41) and 4.26 (0.71), respectively. The time to first recurrence from the first injection was most frequently 3 months. Conclusion: The mTAE regimen of IVA injections for ME due to BRVO effectively improved BCVA and reduced CST, and thus might be an effective therapy to reduce the number of injections and visits.

Immunodeficiency can disrupt normal physiological activity and function. In this study, donkey bone collagen peptide (DP) and its iron chelate (DPI) were evaluated their potential as immunomodulators in cyclophosphamide (Cytoxan®, CTX)-induced Balb/c mice. The femoral tissue, lymphocytes, and serum from groups of mice were subjected to hematoxylin and eosin (H&E) staining, methylthiazolyldiphenyl-tetrazolium bromide (MTT) cell proliferation assays, and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, a non-targeted metabolomics analysis based on UPLC–MS/MS and a reverse transcription polymerase chain reaction (RT-qPCR) technology were used to explore the specific metabolic pathways of DPI regulating immunocompromise. The results showed that CTX was able to significantly reduce the proliferative activity of mouse splenic lymphocytes and led to abnormal cytokine expression. After DP and DPI interventions, bone marrow tissue damage was significantly improved. In particular, DPI showed the ability to regulate the levels of immune factors more effectively than Fe2+ and DP. Furthermore, metabolomic analysis in both positive and negative ion modes showed that DPI and DP jointly regulated the levels of 20 plasma differential metabolites, while DPI and Fe2+ jointly regulated 14, and all 3 jointly regulated 10. Fe2+ and DP regulated energy metabolism and pyrimidine metabolism pathways, respectively. In contrast, DPI mainly modulated the purine salvage pathway and the JAK/STAT signaling pathway, which are the key to immune function. Therefore, DPI shows more effective immune regulation than Fe2+ and DP alone, and has good application potential in improving immunosuppression.

The objective of this study was to investigate the preventive effects of polysaccharides extracted from the roots of Arctium lappa (ALP) against acute lung injury (ALI) models induced by lipopolysaccharide (LPS). The polysaccharides were extracted and characterized, and their anti-inflammatory and antioxidant capacities were assessed. The findings demonstrated that ALP could mitigate the infiltration of inflammatory cells and reduce alveolar collapse in LPS-induced ALI in mice. The expression levels of the pro-inflammatory factor TNF-α decreased, while the anti-inflammatory factor IL-10 increased. Furthermore, the administration of ALP improved the activities of lung antioxidant enzymes, including SOD, GSH, and CAT, and lowered MDA levels. These results suggest that ALP exhibits a preventive effect on ALI and has potential as an alternative treatment for lung injury.

Dietary habits refer to the long-term dietary patterns and habits that an individual forms and maintains in their daily life [...]

Schistosomiasis, typically characterized by chronic infection in endemic regions, has the potential to affect liver tissue and pose a serious threat to human health. Detecting and screening for this disease early on is crucial for its prevention and control. However, existing methods encounter challenges such as low sensitivity, time-consuming processes, and complex sample handling. To address these challenges, we report a soluble egg antigen (SEA)-based functionalized gridless and meander-type AlGaN/GaN high electron mobility transistors (HEMT) sensor for the highly sensitive detection of antibodies to Schistosoma japonicum. Immobilization of the self-assembled membrane on the gate surface was verified using a semiconductor parameter analyzer, scanning electron microscope (SEM), and atomic force microscopy (AFM). The developed biosensor demonstrates remarkable performance in detecting anti-SEA, exhibiting a linear concentration range of 10 ng/mL to 100 μg/mL and a sensitivity of 0.058 mA/log (ng/mL). It also exhibits similar excellent performance in serum systems. With advantages such as rapid detection, high sensitivity, miniaturization, and label-free operation, this biosensor can fulfill the requirements for blood defense.

This innovative study investigates the effects of high-protein diets (milk protein) on the circadian rhythm of hepatic lipid metabolism. We aimed to understand how high-protein interventions regulate biological clock genes, maintain lipid metabolism balance, and affect the circadian rhythm of antioxidant levels in vivo. We divided 120 SPF-class C57BL/6J mice into the control, high-fat/low-protein (HF-LP), and high-fat/high-protein (HF-HP) groups. Mice were sacrificed during active (2 a.m. and 8 a.m.) and rest periods (2 p.m. and 8 p.m.). In the HF-LP group, hepatic lipid anabolic enzymes were consistently expressed at high levels, while key lipolytic enzymes slowly increased after feeding with no significant diurnal differences. This led to an abnormal elevation in blood lipid levels, a slow increase in and low levels of superoxide dismutase, and a rapid increase in malondialdehyde levels, deviating from the diurnal trend observed in the control group. However, high-protein interventions in the HF-HP group restored lipid synthase activity and the expression of key catabolic enzymes, exhibiting a precise circadian rhythm. It also improved the lipid-metabolism rhythm, which was disrupted by the high-fat diet. Overall, high-protein interventions restored the expression of key enzymes involved in lipid metabolism, improving the lipid-metabolism rhythm, which was disrupted by the high-fat diet.

“Foreignization” (taguohua, 他国化) is an important concept in the Variation Theory of Comparative Literature. Through the collision, fusion and heterogeneous absorption of cross-heterogeneous cultural exchanges, the culture and discourse principles of one country are adapted through localization by the receiving country, resulting in what this theory calls “foreignization”. Global Laozegetics continues its traditional interpretive-oriented stance by examining translations of the Daodejing from a Laozegetics perspective, demonstrating a new development in the study of Laozi’s doctrine. Thus, there is a need to explore new perspectives in the research on the German translations of the Daodejing. Taking the cultural imagery Dao and De as examples, this paper explores the background and causes of “foreignization” in German translations of the Daodejing and its impact on the dissemination of Laozi’s doctrine in the German-speaking world, summarizing its formation path and possible problems, with the goal of shedding light on the overseas dissemination of Chinese classics represented by the Daodejing.

Heat shock proteins (HSPs) play critical roles in regulating different mechanisms under high-temperature conditions. HSPs have been identified and well-studied in different plants. However, there is a lack of information about their genomic organization and roles in medicinal plants and fungi, especially in Wolfi-poria cocos (W. cocos). We identified sixteen heat shock proteins (HSPs) in W. cocos and analyzed in terms of phylogenetic analysis, gene structure, motif distribution patterns, physiochemical properties, and expression comparison in different strains. Based on phylogenetic analysis, HSPs were divided into five subgroups (WcHSP100, WcHSP90, WcHSP70, WcHSP60, and WcsHSP). Subgroups WcHSP100s, WcHSP90s, WcHSP70s, WcHSP60, and WcsHSPs were further divided into 3, 2, 3, 1, and 6 subfamilies, respectively. Moreover, the expression profiling of all HSP genes in five strains of W. cocos under different temperature extremes revealed that expression of most HSPs were induced by high temperature. However, every subfamily showed different expression suggesting distinctive role in heat stress tolerance. WcHSP70-4, WcHSP90-1, and WcHSP100-1 showed the highest response to high temperature stress. Heterologous expression of WcHSP70-4, WcHSP90-1, and WcHSP100-1 genes in Escherichia coli enhanced survival rate of E. coli during heat stress. These findings suggest the role of W. cocos heat shock genes in the high temperature stress tolerance.

Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determination of 5-CQA in rat plasma, cerebrospinal fluid (CSF), and brain tissue to investigate whether it could pass through the blood–brain barrier (BBB) and its distribution in the rat brain, and a Caenorhabditis elegans (C. elegans) strain paralysis assay was used to investigate the neuroprotective effect of 5-CQA in different brain tissues. Chromatographic separation of 5-CQA and glycyrrhetinic acid (GA, used as internal standard) was completed in 0.5 min, and the full run time was maintained at 4.0 min. Methodological validation results presented a high accuracy (95.69–106.81%) and precision (RSD ≤ 8%), with a lower limit of quantification of 1.0 ng/mL. Pharmacokinetic results revealed that 5-CQA can pass through the BBB into the CSF, but the permeability of BBB to 5-CQA (ratio of mean AUC0-∞ of CSF to plasma) was only approximately 0.29%. In addition, 5-CQA can penetrate into the rat brain extensively and is distributed with different intensities in different nuclei. A C. elegans strain paralysis assay indicated that the neuroprotective effect of 5-CQA is positively correlated with its content in different brain tissues. In conclusion, our study for the first time explored the BBB pass rate and brain tissue distribution of 5-CQA administered via the tail vein by the UHPLC–MS/MS method and investigated the potential main target area of 5-CQA for neuroprotection, which could provide a certain basis for the treatment of nervous system-related diseases of 5-CQA.

LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H2O2 in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H2O2-induced injury and apoptosis by inhibiting H19.

Aquaculture environment plays important roles in regulating the growth, morphology, nutrition, and flavor of aquatic products. The present study investigated growth, morphology, nutrition, and flavor formation in largemouth bass (Micropterus salmoides) cultured in the ponds with (EM group) and without (M group) the submerged macrophytes (Elodea nuttallii). Fish in the EM group showed a significantly greater body length, higher growth rate, and lower hepatosomatic index than those in the M group (p< 0.05). Moreover, compared with fish in the M group, those in the EM group showed improved muscle quality with significantly elevated levels of crude protein, total free and hydrolysable amino acids, and polyunsaturated fatty acids (p < 0.05). Specifically, certain amino acids related to flavor (Glu, Asp, Ala, and Arg) and valuable fatty acids (C18:2, C18:3n3, C20:3n3, and C22:6) were more abundant in the EM group (p < 0.05). In addition, the levels of 19 volatile (p < 0.05) were significantly higher in the EM group than in the M group. Therefore, E. nuttallii significantly improved growth, morphological traits, nutritional components, and characteristic flavor in largemouth bass, indicating the superior nutritional value and palatability of fish cultured with submerged macrophytes.

The purpose of this study was to investigate the effects of BMP6 on the function of goat ovarian granulosa cells (GCs). The results showed that the exogenous addition of BMP6 did not affect the EdU-positive ratio of ovarian GCs and had no significant effect on the mRNA and protein expression levels of the proliferation-related gene PCNA (p > 0.05). Meanwhile, BMP6 had no significant effect on the cycle phase distribution of GCs but increased the mRNA expression of CDK4 (p < 0.05) and CCND1 (p < 0.01) and decreased the mRNA expression of CCNE1 (p < 0.01). Moreover, BMP6 had no significant effect on the apoptosis rate of GCs and did not affect the mRNA expression levels of apoptosis-related genes BAX, BCL2, and Caspase3 (p > 0.05). Importantly, BMP6 upregulated the secretion of 17 beta-estradiol (E2) and progesterone (P4) in ovarian GCs (p < 0.01). Further studies found that BMP6 inhibited the mRNA expression of 3β-HSD and steroid synthesis acute regulator (StAR) but significantly promoted the mRNA expression of the E2 synthesis rate-limiting enzyme CYP19A1 and the P4 synthesis rate-limiting enzyme CYP11A1 (p < 0.01). Taken together, these results showed that the exogenous addition of BMP6 did not affect the proliferation, cell cycle, and apoptosis of goat ovarian GCs but promoted the secretion of E2 and progesterone P4 in ovarian GCs by upregulating the mRNA expressions of CYP19A1 and CYP11A1.

The selective oxidation of styrene with highly efficient, environmentally benign, and cost-effective catalysts are of great importance for sustainable chemical processes. Here, we develop an in situ self-assembly strategy to decorate Cu-based metal-organic framework (MOF) Cu-BDC-NH2 nanocrystals on Cu2O octahedra to construct a series of Cu2O@Cu-BDC-NH2 catalysts for selective oxidation of styrene. Using H2O2 as green oxidants, the optimized sample of Cu2O@Cu-BDC-NH2-8h could achieve 85% styrene conversion with 76% selectivity of benzaldehyde under a mild condition of 40 °C. The high performance of the as-prepared heterogeneous catalysts was attributed to the well-designed Cu+/Cu2+ interface between Cu2O and Cu-BDC-NH2 as well as the porous MOF shells composed of the uniformly dispersed Cu-BDC-NH2 nanocrystals. The alkaline properties of Cu2O and the –NH2 modification of MOFs enable the reaction to be carried out in a base-free condition, which simplifies the separation process and makes the catalytic system more environmentally friendly. Besides the Cu2O octahedra (od-Cu2O), the Cu2O cuboctahedrons (cod-Cu2O) were synthesized by adjusting the added polyvinyl pyrrolidone, and the obtained cod-Cu2O@Cu-BDC-NH2 composite also showed good catalytic performance. This work provides a useful strategy for developing highly efficient and environmentally benign heterogeneous catalysts for the selective oxidation of styrene.

The lower reaches of the Yellow River is known for the rapid development of industry and agriculture, which has also led to some pollution. However, information about the level of toxic contaminants in the surface waters is lacking in this area. Therefore, five sampling points were set in the lower Yellow River to investigate the distribution of various pollutants and analyze the potential risks. The presence of heavy metals (Heavy metals tested for in this study were: Mercury (Hg), Arsenic (As), Copper (Cu), Chromium (Cr), and Zinc (Zn)) and antibiotics (Antibiotics tested for in this study were: Enrofloxacin (ENR), Ciprofloxacin (CIP), and Norfloxacin (NOR)) in water samples taken from the lower Yellow River were measured to reveal the spatial distribution and risk potential of the compounds. Various water quality parameters (Water quality parameters used in this study were: chemical oxygen demand (COD), biological oxygen demand (BOD5), total phosphorus (TP), and total nitrogen (TN)) were also tested. Study results showed the main surface water pollution components were COD, BOD5, TN, and TP. The average levels were 37.79 mg/L, 16.64 mg/L, 4.14 mg/L, and 0.42 mg/L, respectively. Among the detected metals from the water samples, Hg (LOD-0.1 μg/L) levels were only in line with the surface water class III or worse. Both fish and water samples contained antibiotics. According to an ecological risk assessment conducted along the river, the distribution of pollutants in the waters exhibited a spatial relationship with the land-use pattern in the study region and the Kenli site was the most polluted. Research shows that up-to-date data on the residual levels and distribution characteristics of pollutants in the lower Yellow River could provide valuable baseline data and technical support for relevant government departments and their management going forward.

A highly enantioselective organocatalytic Wolff rearrangement–amidation–Michael–hemiaminalization stepwise reaction is described involving a cyclic 2-diazo-1,3-diketone, primary amine and α,β-unsaturated aldehyde. Product stereocontrol can be achieved by adjusting the sequence of steps in this one-pot multicomponent reaction. This approach was used to synthesize various optically active spirocyclic piperidones with three stereogenic centers and multiple functional groups in good yields up to 76%, moderate diastereoselectivities of up to 80:20 and high enantioselectivities up to 97%.

Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.