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XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel. Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition, pharmacokinetics, and pharmacodynamics. A selectivity test (for "similarity of response") was developed to identify and minimize interference by non-target constituents. Then, an intercept test was developed to fulfill "linearity through zero" for each analyte (absolute ratio of intercept to C response,2%). Using the newly developed assays, we analyzed samples from 33 batches of XueBiJing, manufactured over three years, and found small batch-to-batch variability in contents of the marker constituents (4.1%-14.8%), except for senkyunolide I (26.5%).

Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Indium oxide supported nickel catalyst has been experimentally confirmed to be highly active for CO2 hydrogenation towards methanol. In this work, the reaction mechanism for CO2 hydrogenation to methanol has been investigated on a model Ni/In2O3 catalyst, i.e., Ni4/In2O3, via the density functional theory (DFT) study. Three possible reaction pathways, i.e., the formate pathway, CO hydrogenation and the reverse water–gas-shift (RWGS) pathways, have been examined on this model catalyst. It has been demonstrated that the RWGS pathway is the most theoretically-favored for CO2 hydrogenation to methanol. The complete RWGS pathway follows CO2 + 6H → COOH + 5H → CO + H2O + 4H → HCO + H2O + 3H → H2CO + H2O + 2H → H3CO + H2O + H → H3COH + H2O. Furthermore, it has been also proved that the interfacial oxygen vacancy can serve as the active site for boosting the CO2 adsorption and charge transfer between the nickel species and indium oxide, which synergistically promotes the consecutive CO2 hydrogenation towards methanol.

Background/purpose Growth arrest-specific 6 (Gas6) protein is involved in cell proliferation, differentiation, adhesion, migration in response to inflammatory processes. Human immunodeficiency virus (HIV) infection induces a chronic inflammatory condition and combination of antiretroviral therapy improves immune function and decreases the inflammatory state. The aim of this study was to assess the implications of Gas6 in chronic inflammation status of HIV-infected patients undergoing different third regimens of antiretroviral therapy. The Gas6 may be a marker of chronic inflammation of HIV-infected patients. Methods A total of 356 adult males, including 258 HIV-infected patients and 98 healthy controls, were recruited. The demographic and clinical characteristics of the patients were collected. Laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), hepatitis B and C viruses, and serum biochemistry. Plasma Gas6 concentrations were determined. Results The values of Gas6 were lower in HIV patients compared to healthy subjects (14.3 ± 6.4 vs 21.5 ± 15.2, p = 0.01). HIV patients that received antiviral regimen with abacavir had similar Gas6 level than those who received antiviral regimens with tenofovir (14.3 ± 6.5 vs 13.8 ± 5.9, p = 0.99). HIV patients that received antiviral regimen with protease inhibitors (PIs) had lower Gas6 level (13.1 ± 3.5 vs 14.2 ± 6.6 vs 14.6 ± 6.5, p = 0.03) than those who received antiviral regimens with non-nucleoside reverse transcriptase inhibitors (nNRTIs) and integrase inhibitors (INSTIs), respectively. Conclusions Decreased plasma Gas6 concentrations were observed in HIV patients. Gas6 levels are associated with different third regimen of highly active antiretroviral therapy. Gas6 may represent a unique marker for assessing the chronic inflammation state difference among cART regimens in HIV patients.

Traditional approaches to the directed evolution of genes of interest (GOIs) place constraints on the scale of experimentation and depth of evolutionary search reasonably achieved. Engineered genetic systems that dramatically elevate the mutation of target GOIs in vivo relieve these constraints by enabling continuous evolution, affording new strategies in the exploration of sequence space and fitness landscapes for GOIs. We describe various in vivo hypermutation systems for continuous evolution, discuss how different architectures for in vivo hypermutation facilitate evolutionary search scale and depth in their application to problems in protein evolution and engineering, and outline future opportunities for the field.

Kadsura belongs to the Schisandroideae subfamily of Magnoliaceae. Plants from genus Kadsura are widely distributed in the South and Southwest of China. The plants of the genus are widely used as folk medicine for a long time in history, with the functions of relieving pain, promoting ‘qi’ circulation, activating blood resolve stasis, and applications in the treatment of rheumatoid arthritis and gastroenteric disorders. Lignans are the primary characteristic constituents with various biological activities of plants from genus Kadsura. This paper summarized 81 lignans isolated from the plants of genus Kadsura over the past eight years (from 2014 to 2021), which belong to five types: dibenzocyclooctadienes, spirobenzofuranoid dibenzocyclooctadienes, aryltetralins, diarylbutanes and tetrahydrofurans. Each type of these lignans possess typical characteristics in proton magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR) spectra, the NMR regularities of these types of lingans were summarized, which provided a useful reference for the structural analysis of lignans. The relationships between lignans and pharmacodynamics were also systematically analyzed, lignans were predicted to be the quality markers (Q-marker) of Kadsura genus.

Enzyme reaction has been accepted widely in numerous applications owing to the high efficiency and stereo-selectivity, as well as simple preparation by gene engineering. However, the fragility and complex purification process of the enzyme are long-standing problems which limit the large-scale application. One possible solution may be the enzyme immobilization. As one type of porous material with high loading capacity and designable functionality, Metal-Organic Frameworks (MOFs) are ideal choices for the immobilization of enzyme with a considerable interest in recent years. In this study, d-amino acid transaminase (DAT), an important enzyme for industrial synthesis of d-Ala, was covalently immobilized on the surface of a star MOFs material, UiO-66-NH2. Interestingly, we found that the nanoscale hybrid enzyme UiO-66-NH2-Gd-DAT not only maintained the high catalytic efficiency but also got rid of the interference of polluting enzymes, which meant that we could obtain efficient and stereo-selective immobilized enzyme without complex purification process. In general, our findings demonstrated that using UiO-66-NH2 might be a promising strategy to immobilize enzyme and produce effective biocatalyst with high activity and stereo-selectivity.

CO2 hydrogenation to methanol is of great significance for the emission control and utilization of CO2. In this work, the Rh/In2O3 catalyst with high Rh dispersion was prepared by deposition-precipitation method. The catalyst characterization demonstrates that the highly dispersed Rh species promotes the dissociative adsorption and spillover of hydrogen, which further enhances not only the formation of surface oxygen vacancy of In2O3 but also CO2 adsorption and activation. Enhanced activity was thereby achieved for selective hydrogenation of CO2 to methanol. A CO2 conversion of 17.1 % with methanol selectivity of 56.1 %, corresponding to a methanol space time yield (STY) up to 0.5448 gMeOH h−1 gcat−1, has been obtained under 300 °C, 5 MPa, 76/19/5 of H2/CO2/N2 (molar ratio) and 21,000 cm3 h−1 g−1 of gas hourly space velocity. Under the same reaction condition, the CO2 conversion is only 9.4 % with a methanol STY of 0.3402 gMeOH h−1 gcat−1 over In2O3. The methanol selectivity can be even higher than 70 % at the reaction temperatures below 275 °C for Rh/In2O3 catalyst.

The applications of supramolecular metal-peptide assemblies as catalyst or catalyst precursor have recent attracted increasing attentions. In this work, a fragment of the amyloid β-peptide, NH2-KLVFF-COOH, was assembled into nanofilms with encapsulated Pd, Pt and Au nanoparticles (NPs) via a one-step room temperature electron induction method. The effects of building block, intermolecular interaction, driving force and side-chain on the assembly were investigated. The assembly mechanism was thereby proposed. The crosslinking of peptide monomers results in mainly random and unordered structures. The obtained metal-peptide assemblies are extremely stable in water at neutral pH for long term. However, the metal NPs are able to be responsively released under basic and reductive conditions. The released NPs show a high activity to catalyze the reduction of 4-nitrophenol. The present studies on assembly mechanism and responsive release will be helpful for the design of organic skeletons and also for the future development of peptide stabilized metallic NPs with applications beyond catalysts.

Panax japonicus, which in the Tujia dialect is known as “Baisan Qi” and “Zhujieshen”, is a classic “qi” drug of Tujia ethnomedicine and it has unique effects on disease caused by “qi” stagnation and blood stasis. This paper serves as the basis of further scientific research and development of Panax japonicus. The pharmacology effects of molecular pharmacology were discussed and summarized. P. japonicus plays an important role on several diseases, such as rheumatic arthritis, cancer, cardiovascular agents, and this review provides new insights into P. japonicus as promising agents to substitute ginseng and notoginseng.

Objective The left subclavian artery (LSA) origin can be intentionally covered by stent grafts, to provide adequate proximal landing zones during thoracic endovascular repair for Stanford type B aortic dissections (TBADs). To preserve the LSA, a novel single branched stent graft, named “Castor” was designed and a clinical trial conducted to investigate its suitability. Methods From April 2013 to March 2015, 73 patients with TBAD were treated by Castor stent grafts at 11 Chinese tertiary hospitals as part of a single arm prospective clinical trial. There were 50 acute ( 2 weeks [31.5%]). Results The technical success rate was 97% (n = 71/73). The two failures were caused by occlusion of the branch section of the stent graft. There were four intra-operative endoleaks (two type Ia, two type B from the LSA). The endoleak rate was 5% (n = 4/73). There was one in hospital death and no major complications. The median follow up time was 61 months (range 48–72 months). The mortality was 5% (n = 4/73) within one year and 7% within six years (n = 5/73). Two deaths were of unknown cause and three were not related to the aorta. Two new entry tears were found on the proximal or distal edge of the stent graft and were retreated endovascularly. Six occlusions of the branch section of the Castor stent graft were found, and the follow up patency rate of the branch section was 93% (n = 63/68). Two intra-operative endoleaks were left during follow up and eventually disappeared according to the latest computed tomography angiograms. Conclusion For patients with TBADs needing anchoring proximal to the origin of LSA, the Castor single branched stent graft may provide an easily manipulated, safe, and effective endovascular treatment.

The purposes of this study are to assess the COVID-19 pandemic's impacts on the dairy industries in China and the United States and to derive policy recommendations for enhancing the diary industries' resilience to pandemics and other market shocks. Specifically, data from the two nations are used to analyze and compare the mechanisms through which the pandemic has affected their dairy industries and to discuss potential lessons from their experiences. The findings suggest that this pandemic has heavily affected the dairy industries in both China and the United States through similar mechanisms, such as decreased farmgate milk prices, disruption and difficulties of moving milk within the supply chains, worker shortages, increased production costs, and lack of operating capital. There were also significant differences in the affecting mechanisms between the two nations, including transportation difficulties from widespread road closures and significant reduction in holiday sales of dairy products in China, and the shutdown of many dairy processors in the United States due to the closing of schools, restaurants, and hotels. While government financial reliefs are highly needed to help many dairy farms and processors survive this pandemic in the short term, the dairy industries and governments need to work together to develop long-term strategies and policies to balance the industries' efficiency and flexibility, product specialization and diversification, supply chain integration and local food systems, and market mechanisms and policy regulations and interventions.

An In2O3 supported nickel catalyst has been prepared by wet chemical reduction with sodium borohydride (NaBH4) as a reducing agent for selective hydrogenation of carbon dioxide to methanol. Highly dispersed Ni species with intense Ni-In2O3 interaction and enhanced oxygen vacancies have been achieved. The highly dispersed Ni species serve as the active sites for hydrogen activation and hydrogen spillover. Abundant H adatoms are thereby generated for the oxygen vacancy creation on the In2O3 surface. The enhanced surface oxygen vacancies further lead to improved CO2 conversion. As a result, an effective synergy between the active Ni sites and surface oxygen vacancies on In2O3 causes a superior catalytic performance for CO2 hydrogenation with high methanol selectivity. Carbon monoxide is the only by product detected. The formation of methane can be ignored. When the reaction temperature is lower than 225 °C, the selectivity of methanol is 100%. It is higher than 64% at the temperature range between 225 °C and 275 °C. The methanol selectivity is still higher than 54% at 300 °C with a CO2 conversion of 18.47% and a methanol yield of 0.55 gMeOH gcat−1 h−1 (at 5 MPa). The activity of Ni/In2O3 is higher than most of the reported In2O3-based catalysts.

Uracil-DNA glycosylases (UDGs) are conserved DNA-repair enzymes that can be found in many species, including herpesviruses. Since they play crucial roles for efficient viral DNA replication in herpesviruses, they have been considered as potential antiviral targets. In our previous work, Staphylococcus aureus SAUGI was identified as a DNA mimic protein that targets UDGs from S. aureus, human, Herpes simplex virus (HSV) and Epstein-Barr virus (EBV). Interestingly, SAUGI has the strongest inhibitory effects with EBVUDG. Here, we determined complex structures of SAUGI with EBVUDG and another γ-herpesvirus UDG from Kaposi's sarcoma-associated herpesvirus (KSHVUDG), which SAUGI fails to effectively inhibit. Structural analysis of the SAUGI/EBVUDG complex suggests that the additional interaction between SAUGI and the leucine loop may explain why SAUGI shows the highest binding capacity with EBVUDG. In contrast, SAUGI appears to make only partial contacts with the key components responsible for the compression and stabilization of the DNA backbone in the leucine loop extension of KSHVUDG. The findings in this study provide a molecular explanation for the differential inhibitory effects and binding strengths that SAUGI has on these two UDGs, and the structural basis of the differences should be helpful in developing inhibitors that would interfere with viral DNA replication.

Over the past few decades, there have been many advances in pediatric surgery, some using new devices (eg, VEPTR, MAGEC rods) and others using less invasive approaches (eg, Nuss procedure, endoscopic cranial suture release, minimally invasive tethered cord release). Although many of these procedures were initially met with caution or skepticism, continued experience over the past few decades has shown that these procedures are safe and effective. This article reviews the anesthetic considerations for these conditions and procedures.

Summary UTX, a H3K27me3 demethylase, plays an important role in mouse brain development. However, so little is known about the function of UTX in human neural differentiation and dendritic morphology. In this study, we generated UTX-null human embryonic stem cells using CRISPR/Cas9, and differentiated them into neural progenitor cells and neurons to investigate the effects of UTX loss of function on human neural development. The results showed that the number of differentiated neurons significantly reduced after loss of UTX, and that the dendritic morphology of UTX KO neurons tended to be simplified. The electrophysiological recordings showed that most of the UTX KO neurons were immature. Finally, RNA sequencing identified dozens of differentially expressed genes involved in neural differentiation and synaptic function in UTX KO neurons and our results demonstrated that UTX regulated these critical genes by resolving bivalent promoters. In summary, we establish a reference for the important role of UTX in human neural differentiation and dendritic morphology., Graphical Abstract, Highlights • Loss of UTX in hESCs reduces their neural differentiation potential • The dendritic morphology of UTX KO neurons tends to be simplified • UTX regulates human neural development depending on its demethylation • UTX regulates the expression of genes by resolving bivalent promoters, In this article, Liu and colleagues show that the deletion of UTX in hESCs leads to the decline of their ability to differentiate into neurons, and the decrease of neurite complexity of neurons. UTX regulates dozens of genes involved in neural differentiation and synaptic function by resolving bivalent promoters depending on its demethylation.

The 1,3-dipolar cycloaddition reaction of dimethyl hex-2-en-4-ynedioate with azomethine ylides derived from reaction of l -proline with various isatins in methanol selectively resulted in the formation of functionalized spiro[indoline-3,3′-pyrrolizine]acrylates as main products and spiro[indoline-3,3′-pyrrolizine]propiolates as minor products. This result indicated that the electron-deficient alkyne has higher reactivity than that of electron-deficient alkene in 1,3-dipolar cycloaddition reaction.

Although the recognition of facial expressions seems automatic and effortless, discrimination of expressions can still be error prone. Common errors are often due to visual similarities between some expressions (e.g., fear and surprise). However, little is known about the neural mechanisms underlying such a confusion effect. To address this question, we recorded the magnetoencephalography (MEG) while participants judged facial expressions that were either easily confused with or easily distinguished from other expressions. The results showed that the fusiform face area (FFA), rather than the posterior superior temporal sulcus (pSTS), played a preponderant role in discriminating confusable facial expressions. No difference between high confusion and low confusion conditions was observed on the M170 component in either the FFA or the pSTS, whilst a difference between two conditions started to emerge in the late positive potential (LPP), with the low confusion condition eliciting a larger LPP amplitude in the FFA. In addition, the power of delta was stronger in the time window of LPP component. This confusion effect was reflected in the FFA, which might be associated with the perceptual-to-conceptual shift.

Structured porous carbon materials have been extensively applied for catalyst, sensor, adsorbent, energy storage materials and many others. However, the preparation of such carbon materials in a controllable way remains a significant challenge. In this work, 3D printing has been employed to prepare porous carbon structures with tailorable pore sizes. A starch/gelatin ink has been applied as carbon source with SiO2 monodispersed spheres as hard template. The process exhibits an excellent printing accuracy. Controllable meso and macro structures can be thereby obtained. The printed monolithic structures have been used as metal-free catalysts for the selective oxidation of benzyl alcohol, as an illustration. The monolithic and meso/macro-porous structure has a remarkable influence on the reaction rate. A high conversion with high benzaldehyde selectivity has been achieved. The 3D printing strategy provides us a simple, low cost and reliable way of fabricating carbon structures with designable meso/macro-pores, which is promising for many other applications beyond catalysis.

Tyramine (TA), a biogenic monoamine, plays various important physiological roles including immunological regulation in invertebrates. In this study, the effects of TA on the regulation of immune resistance, carbohydrate metabolism and biogenic monoamine, as well as its signaling pathway in Macrobrachium rosenbergii were determined. Results showed that total haemocyte count, hyaline cells, semigranular cells, and phenoloxidase activity per 50 μL of haemolymph and per granulocyte (the sum of semigranular and granular cells) at 0.5 h as well as phagocytic activity and clearance efficiency to Lactococcus garvieae at 1 h of prawn injected with TA at 1 nmol prawn−1 significantly increased, but the significantly decreased plasma lysozyme activity, phagocytic activity, clearance efficiency, and haemolymph glucose and dopamine were observed in prawn injected with TA at 10 nmol prawn−1 for 0.5 h. Respiratory bursts and haemolymph lactate in two TA-injection treatments at 0.5 h and 0.5–1 h, respectively, were significantly higher than those of the saline control, and in addition, TA depressed dopamine release in a dose-dependent manner after 0.5 h of TA injection. All the examined parameters returned to control levels after prawn injected with TA for 2 h. The inhibited effect of TA (at 10 nmol prawn−1 injection) on the phagocytic activity and clearance efficiency to pathogens was blocked by prazosin (an α1 adrenoceptors antagonist). For prawn received TA for 1 h then challenged with Lactococcus garvieae at 2 × 105 colony-forming units prawn−1, the survival ratio of TA 1 nmol prawn−1-injected prawn significantly increased by 20%, compared to the saline-challenged control or TA 10 nmol prawn−1-injected prawn after 144 h of challenge. These results suggested that the level of dopamine release suppression regulated by TA resulted in the immunoenhancing or immunosuppressive effects in prawn, and the signaling pathways of TA in mediating immune function were through octopamine (OA)/TA receptors.

Summary Objective Current research is controversial about whether metformin can improve the survival rate of patients with colon cancer. Therefore, we conducted a meta-analysis to identify the association between metformin and the survival rate of colorectal cancer (CRC) patients with type II diabetes. Methods We conducted a search in databases including Pubmed, EMBASE and Cochrane Library. All articles were published in the last decade, and the quality of each study was evaluated by the Newcastle-Ottawa Scale. Odds ratios (ORs) and its corresponding 95% confidence intervals (CIs) for each study were calculated and summary relative risk estimates with corresponding 95% CIs were generated using the random-effects model. Heterogeneity and publication bias were assessed. Results Ten articles were included in this meta-analysis. The included articles were all cohort studies. In a pooled analysis of all studies, metformin using was associated with increased overall survival (OS) rate (OR, 0.54; 95% CI, 0.47 to 0.63) and cancer-specific survival (CS) rate (OR 0.59; 95% CI 0.43 to 0.82) of CRC patients with diabetes. We found that the effect of metformin is associated with geographical region through subgroup meta-analysis. Conclusions Metformin using was associated with an increased OS rate and CS rate of colorectal cancer.

Background Sacrifice of the internal iliac artery (IIA) may result in ischemic manifestations after aortoiliac aneurysm (AIA) or common iliac artery aneurysm (CIAA) endovascular repair. This study sought to evaluate the safety and efficacy of a new Iliac Bifurcation Stent Graft (IBSG; Lifetech Scientific, Shenzhen, China) system for revascularization of the IIA. Methods Patients who underwent implantation of the IBSG at 8 centers in China from September 2015 to June 2018 were enrolled. Clinical and computed tomography angiography follow-up assessments were conducted at 30 and 180 days postoperatively. The primary end point was the IIA patency rate of the IBSG device at 180 days postoperatively. Secondary end points comprised the postoperative technical success rate and clinical success rate at 30 and 180 days. Descriptive statistics and the Clopper-Pearson exact method were used to analyze the data. Results Seventy-three patients (mean age, 69.6 years; 91.8% men) were eligible for this trial, and 59 patients were eligible for primary effectiveness end-point analysis. AIA was present in 55 patients (75.34%) and CIAA in 18 patients (24.66%). The iliac artery aneurysms were unilateral in 69 patients (94.52%) and bilateral in 4 patients (5.48%). Overall technical success was 89.04% (65 of 73 patients). IIA patency at 180 days was 96.61% (57 of 59 patients). Sexual dysfunction occurred in 1 patient (1.69%), and 2 patients (3.39%) experienced buttock claudication. There was no mortality, type III endoleak, stent migration, kinking, or fracture during the procedure and follow-up. Conclusions The IBSG implantation system is a safe and effective technique for IIA preservation during AIA or CIAA endovascular repair. The high technical success rate, IIA patency rate, and low complication rate are promising. Follow-up will be continued for 5 years to confirm the durability of the device.

Cytokinins (CKs), primarily trans-zeatin (tZ) and isopentenyladenine (iP) types, play critical roles in plant growth, development, and various stress responses. Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP-binding cassette transporter subfamily G14 (AtABCG14) has been well studied; however, less is known about the biochemical properties of AtABCG14 and its transporter activity toward iP-type CKs. Here we reveal the biochemical properties of AtABCG14 and provide evidence that it is also required for long-distance transport of iP-type CKs. AtABCG14 formed homodimers in human (Homo sapiens) HEK293T, tobacco (Nicotiana tabacum), and Arabidopsis cells. Transporter activity assays of AtABCG14 in Arabidopsis, tobacco, and yeast (Saccharomyces cerevisiae) showed that AtABCG14 may directly transport multiple CKs, including iP- and tZ-type species. AtABCG14 expression was induced by iP in a tZ-type CK-deficient double mutant (cypDM) of CYP735A1 and CYP735A2. The atabcg14 cypDM triple mutant exhibited stronger CK-deficiency phenotypes than cypDM. Hormone profiling, reciprocal grafting, and

Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed.This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug.The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines.Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation.Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.

An efficient dual-ligand zeolitic imidazolate framework ZIF-8-90 was fabricated for the synthesis of five-membered cyclic carbonate from CO2 and epichlorohydrin (ECH) in the absence of co-catalysts and solvents. The effects of various reaction parameters were studied. The dual-ligand ZIF-8-90 showed very high selectivity (up to 99%). ZIF-8-90 exhibited better catalytic ability with lower cost than ZIF-90 and enhanced framework stability with significantly improved selectivity compared to ZIF-8. Moreover, the catalyst has been successfully reused for three cycles with negligible decrease in the catalytic activity. A plausible mechanism for the ZIF-8-90 catalyzed ECH−CO2 cycloaddition under solvent-free and co-catalyst-free has been proposed.

Oxidative stress and cardiomyocyte apoptosis contributed to the progression of doxorubicin (Dox)-induced cardiotoxicity. Recent studies identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that functioned as a key regulator in stress-induced cardiac injury. The present study aimed to investigate the role and possible mechanism of miR-22 on Dox-induced oxidative stress and cardiomyocyte apoptosis. Mice were exposed to reduplicative injections of Dox (i.p., 4 mg/kg) weekly for consecutive 4 weeks to generate Dox-induced cardiotoxicity. Herein, we found that miR-22 level was significantly increased in murine hearts subjected to chronic Dox treatment. MiR-22 inhibition attenuated oxidative stress and cardiomyocyte apoptosis in vivo and in vitro, thereby preventing Dox-induced cardiac dysfunction. Mechanistically, we observed that miR-22 directly bound to the 3′-UTR of Sirt1 and caused SIRT1 downregulation. Conversely, miR-22 antagomir upregulated SIRT1 expression and SIRT1 inhibitor abolished the beneficial effects of miR-22 antagomir. In conclusion, miR-22 inhibition prevented oxidative stress and cardiomyocyte apoptosis via upregulating SIRT1 and miR-22 might be a new target for treating Dox-induced cardiotoxicity.

Pure egg albumen fiber has potential applications in the food industry, biomedicine, drug-controlled release systems, and as a tissue engineering scaffold. However, this type of fiber has not been successfully prepared so far. In this study, pure egg albumen fiber was successfully prepared using the simple method of coaxial wet-spinning with a polysulfone (PSU) hollow fiber as a template. PSU solution and egg albumen solution were extruded into a coagulation bath of distilled water to fabricate egg albumen/PSU fiber, in which the egg albumen solution was wrapped up by the outside PSU layer. Continuous pure egg albumen fiber was obtained after heat treatment in hot water and removal of the PSU layer by dissolution in N, N -dimethylformamide. The prepared continuous egg albumen fiber with good gloss could be lifted along the axial direction. Scanning electron micrographs revealed a dense structure. This successful preparation of pure egg albumen fiber will enable the manufacture of egg albumen fiber composites with excellent application potential for tissue engineering scaffolds.

A revolution in cellular measurement technology is underway. Whereas prior studies have been able to analyze only the averaged outputs from renal tissue, we now can accurately monitor genome-wide gene expression, regulation, function, cellular history, and cellular interactions in thousands of individual cells in a single experiment. These methods are key drivers in changing our previous morphotype-based organ and disease descriptions to unbiased genomic definitions and therefore improving our understanding of kidney development, homeostasis, and disease.

Modifying the nanostructures and chemical compositions provides an opportunity of developing the effective and inexpensive hydrogen evolution reaction (HER) electrocatalysts. Herein, porous transition metal doped tungsten phosphide (M-WP, M=Mo, Co) catalysts have been developed as enhanced HER electrocatalysts in comparison with pristine WP. Owing to the incorporated transition metals, the as-prepared M-WP nanomaterials exhibit porous nanostructures, abundant active sites and reduced charge transfer resistances. Density functional theory (DFT) calculations further demonstrate that the Co dopant simultaneously facilitates the water dissociation step and optimizes the hydrogen adsorption free energy during the entire HER process. Consequently, the Co-WP catalyst shows efficient and stable HER performance over wide pH range. This work demonstrates how metal dopants promote the HER kinetics and develops the strategy for further designing non-precious metal based nanomaterials for energy conversion and electrocatalysis.

CO methanation over supported Ni catalysts has recently attracted increasing attentions. However, the low temperature activity and stability of Ni catalysts still need to be improved. In this work, a dielectric barrier discharge (DBD) plasma decomposition of nickel nitrate was performed at atmospheric pressure and around 150 °C. Followed by the hydrogen reduction thermally at 500 °C, a highly dispersed Ni/ZrO2 catalyst with intensified Ni-ZrO2 interaction and significantly improved activity for CO methanation was obtained. The DBD plasma decomposed catalyst effectively promotes CO dissociation as well as further hydrogenation. In addition, more reactive atomic carbon is formed on the Ni active sites. Such carbon species can be quickly removed by H2 gasification, keeping the Ni surface clean. A better balance between CO dissociation and carbon gasification has been achieved with enhanced carbon resistance. Therefore the DBD plasma decomposed catalyst can remain active under lower H2/CO ratios, while the calcined catalyst needs higher H2/CO feed ratio to overcome the catalyst deactivation.

Curvulamine is a novel framework alkaloid with prominent antibacterial and acetylcholinesterase inhibitory activities produced by marine fungus, Curvularia sp. IFB-Z10. However, the low yield severely restricts its further pharmaceutical researches and applications. The study was aimed to enhance curvulamine production based on CaCl2 addition strategy and further clarify the underlying regulation mechanism of Ca2+. In this work, the optimal addition conditions of CaCl2 were firstly obtained, and curvulamine production achieved 42.96 mg/L under supplying 5 mM CaCl2 at 0 h, which was 3.33-fold that of control in shake flask. It was further found that cytosolic Ca2+ level was markedly increased through calcium channel under CaCl2 stimulation. Relatively high intracellular Ca2+ level could induce fungus to principally form pellets with small diameter and compact structure (morphology), and significantly up-regulate the transcriptional and expression levels of key biosynthetic genes, which collectively promoted curvulamine synthesis. Finally, CaCl2 addition strategy was successfully applied in 5-L bioreactor. This work provided an effective regulation strategy to improve curvulamine production in submerged fermentation of Curvularia sp. and it would facilitate further research on the synthesis regulation of secondary metabolites from other marine filamentous fungi.

Summary EED (embryonic ectoderm development) is a core component of the Polycomb repressive complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27) during the process of self-renewal, proliferation, and differentiation of embryonic stem cells. However, its function in the mammalian nervous system remains unexplored. Here, we report that loss of EED in the brain leads to postnatal lethality, impaired neuronal differentiation, and malformation of the dentate gyrus. Overexpression of Sox11, a downstream target of EED through interaction with H3K27me1, restores the neuronal differentiation capacity of EED-ablated neural stem/progenitor cells (NSPCs). Interestingly, downregulation of Cdkn2a, another downstream target of EED which is regulated in an H3K27me3-dependent manner, reverses the proliferation defect of EED-ablated NSPCs. Taken together, these findings established a critical role of EED in the development of hippocampal dentate gyrus, which might shed new light on the molecular mechanism of intellectual disability in patients with EED mutations., Graphical Abstract, Highlights • EED ablation in NSPCs leads to postnatal lethality and malformation of dentate gyrus • SOX11 overexpression restores the differentiation capacity of EED-ablated NSPCs • Downregulation of CDNN2A reverses the proliferation defect of EED-ablated NSPCs • EED regulates the expression of downstream target Sox11 in an H3K27me1-dependent manner, In this article, Chang-Mei Liu and colleagues show that EED is necessary for neuronal differentiation in the dentate gyrus, by targeting the downstream target Sox11 through interaction with H3K27me1. These data established a critical role of EED in the development of hippocampal dentate gyrus, which might shed new light on understanding molecular mechanism of intellectual disability in patients with EED mutations.