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The rational design and preparation of bifunctional electrocatalysts with pleasant oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance is crucial for extensive commercial applications of rechargeable Zn–air batteries (ZABs). Herein, we report a simple method to obtain multi-metal (Fe, Ni, Zn) embedded in N-doped carbon sheets entangled with carbon nanotubes (CNTs) as superior oxygen electrocatalysts (FeNi-NCS-2). The resultant FeNi-NCS-2 exhibits an impressive electrochemical performance, providing a reversible oxygen overpotential as low as 0.758 V. The ZAB with FeNi-NCS-2 as the air cathode shows a promising capacity of 639.71 mAh g−1 at 20 mA cm−2, a power density of 109.8 mW cm−2 and cycling stability of over 130 cycles at 10 mA cm−2 with an energy efficiency of about 55%, superior to the ZAB based on Pt/C–IrO2. The satisfactory electrocatalytic performance is mainly due to the Fe, Ni-based nanoparticles protected by graphitic carbon layers, hierarchical porous lamellar structures that promote the accessibility between the active centers and the electrolyte as well as self-growing tangled carbon nanotubes that provide fast transmission channels. This study presents a facile way for the synthesis of highly efficient ORR/OER bifunctional electrocatalysts for high-performance rechargeable ZABs.

Cardiac troponin I (cTnI) is a specific biomarker of acute myocardial infarction (AMI). However, cTnI detection kits prepared with antibodies have many defects. Nucleic acid aptamers are sequences of single-strand DNA or RNA that can overcome the deficiency of antibodies. Herein, sandwich ELONA methods were established based on aptamers. Two selected ssDNA aptamers (Apt3 and Apt6) showed high binding affinity and sensibility (Apt3: Kd = 1.01 ± 0.07 nM, Apt6: k = 0.68 ± 0.05) and did not bind to the same domain of cTnI. Therefore, these two aptamers can be applied to the ELONA methods. The detection range of cTnI using the dual-aptamer sandwich ELONA method was 0.05-200 ng/mL, and the bioanalytical method verification results can meet the national standard of Chinese Pharmacopoeia (2020 Edition). There was no difference between results of the dual-aptamer sandwich ELONA method and the diagnostic results of serum obtained from 243 people (P = 0.39, P ˃ 0.05). The sensitivity and specificity of the ELONA with cTnI in serum were 96.46% and 93.85%, respectively. Compared with the FICA kit, which is clinically used, the consequences of ELONA method are closer to the diagnostic results. This study suggests that the aptamers Apt3 and Apt6 have high affinity and strong specificity and that the dual-aptamer sandwich ELONA method has a wide detection range and can be used to determine cTnI in serum, with potential applications in the diagnosis of AMIs.

A double-stranded RNA (dsRNA) mycovirus from the phytopathogenic fungus Alternaria alternata, which causes watermelon leaf blight, was characterized. The genome of this virus has eight dsRNA segments, ranging from 1039 bp to 2398 bp. DsRNAs 1-6 each contain a single large open reading frame (ORF), while dsRNAs 7 and 8 each dsRNA contain two ORFs. The RNA-dependent RNA polymerase (RdRp) encoded by dsRNA1 and the viral methyltransferase encoded by dsRNA3 share 97.6% and 98.9% amino acid sequence identity, respectively, with the corresponding proteins of Plasmopara viticola lesion associated polymycovirus 1. The dsRNA5-encoded proline-alanine-serine-rich protein shows 48.1% sequence identity to that of Beauveria bassiana polymycovirus 3. The proteins encoded on dsRNAs 2, 4, and 8 have 99.7%, 98.2%, and 65.1% sequence identity, respectively, to the corresponding proteins of a mycovirus identified in Alternaria sp. FA0703 (AltR1). The proteins encoded by dsRNAs 6 and 7 do not match any known proteins of mycoviruses. Phylogenetic analysis of the RdRp domain showed that the virus clustered with members of the family Polymycoviridae. Based on these characteristics, the mycovirus was identified as a polymycovirus and designated as "Alternaria alternata polymycovirus 1" (AaPmV1). This is the first report of a polymycovirus associated with A. alternata.

Single-atom catalysts are a relatively new type of catalyst active for numerous reactions but mainly for chemical transformations performed at low or intermediate temperatures. Here we report that singly dispersed Rh1O5 clusters on TiO2 can catalyze the partial oxidation of methane (POM) at high temperatures with a selectivity of 97% for producing syngas (CO + H2) and high activity with a long catalytic durability at 650 °C. The long durability results from the substitution of a Ti atom of the TiO2 surface lattice by Rh1, which forms a singly dispersed Rh1 atom coordinating with five oxygen atoms (Rh1O5) and an undercoordinated environment but with nearly saturated bonding with oxygen atoms. Computational studies show the back-donation of electrons from the dz2 orbital of the singly dispersed Rh1 atom to the unoccupied orbital of adsorbed CHn (n > 1) results in the charge depletion of the Rh1 atom and a strong binding of CHn to Rh1. This strong binding decreases the barrier for activating C-H, thus leading to high activity of Rh1/TiO2. A cationic Rh1 single atom anchored on TiO2 exhibits a weak binding to atomic carbon, in contrast to the strong binding of the metallic Rh surface to atomic carbon. The weak binding of atomic carbon to Rh1 atoms and the spatial isolation of Rh1 on TiO2 prevent atomic carbon from coupling on Rh1/TiO2 to form carbon layers, making Rh1/TiO2 resistant to carbon deposition than supported metal catalysts for POM. The highly active, selective, and durable high-temperature single-atom catalysis performed at 650 °C demonstrates an avenue of application of single-atom catalysis to chemical transformations at high temperatures.

Compared with high molecular weight chitosan (HMWC), low molecular weight chitosan (LMWC) has better solubility and biological activity. However, there is no quick and environmentally friendly to prepare low molecular chitosan. In this study, microwave induced plasma desorption/ionization (MIPDI) was used for the first time to prepare LMWC through the degradation processes of HMWC. The results showed that MIPDI has the most abundant ∙OH content at the gas-liquid interface, and the active particles represented by ∙OH can degrade chitosan with a molecular weight of 540 KDa into soluble chitosan (≤ 10 KDa), and the yield of soluble chitosan can reach 61% in 60 min. Moreover, a series of characterization results showed that the chain structure and crystal structure gradually degraded as the treatment time increased while the chemical structure of chitosan did not change significantly. Antibacterial experiments also indicated that the antimicrobial property of LMWC obtained by MIPDI degradation was improved. In short, this method has proven to be a new, fast and green processing method for the preparation of low molecular chitosan.

Objective The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC). Methods In this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq. Results AJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P Conclusion Ethanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.

An electrochromic supercapacitor is a new type of multifunctional device. It can store energy, change its optical properties, and its color can intuitively reflect the energy storage of the device in real time. This study focused on W18O49 nanowires (WNS) and polyaniline (PANI) electrochromic materials and their thin-film electrodes. Graphene oxide was incorporated in the process of solvothermal preparation of WNS and graphene/W18O49 nanowires composite (rGO–WNS) was obtained. Compared with WNS, the electron transport capability of rGO–WNS is improved, which effectively reduce the discoloration time from 7 to 4 s and the coloring time from 10 to 2 s. In addition, the coloration efficiency has also improved from 45.37 to 52.72 cm−2·C−1, however, the optical modulation amplitude of the composite is reduced from 35 to 20% due to the obstruction of graphene to the transmittance. A characteristic pseudocapacitive behavior is observed for rGO–WNS and PANI electrodes, which were assembled in pairs to form an EC supercapacitor (ECSC) device. With the voltage increased from − 0.2 to 1.4 V, the color of ECSC varies among light green, dark green, light blue and dark blue.

This research first verified that prokaryotic algae are more sensitive to toxicity of CuO nanoparticles (CuO NPs) than eukaryotic algae and that CuO NPs damaged photosynthesis of prokaryotic algae (Arthrospira sp.) but had no effect on respiration. The Cu2+ released by CuO NPs caused a bending deformation of the thylakoid, which was an important cause of the decline in photosynthetic capacity. In addition, the D1 protein was the most susceptible site to CuO NPs. The degradation of D1 protein reduced photosynthetic electron transport, which enhanced the excess excitation energy to cause the accumulation of reactive oxygen species (ROS) to further result in oxidative stress on algae. Dissolved organic matter (DOM) increased the toxicity of CuO NPs to photosynthesis of Arthrospira sp. The damage of photosynthesis caused by CuO NPs is an important reason why CuO NPs have a serious toxicity to algae.

Transition metal chalcogenides are attractive electrocatalysts for oxygen evolution reaction (OER) or hydrogen evolution reaction (HER) due to their natural abundance and diverse structure. Herein, nickel sulfides (Ni3S2) and nickel/cobalt sulfides nanohybrid have been in situ fabricated on nickel foam (NF) by a facile hydrothermal method with sodium sulfide (Ss), L‐cysteine (Lc) or thiourea (Tu) as a sulfur source, respectively. The results show that sulfur source has a great influence on the phase structure, morphology and electrocatalytic performance of transition metal sulfides. The nickel sulfide with the sodium sulfide as a sulfur source (NiSs) shows better HER and OER activity in 1 M KOH. With the Co‐doping, three‐dimensional honeycomb‐like NiCoSs nanosheet clusters exhibits the enhanced electrocatalysis properties with overpotentials of only 168 mV at 10 mA cm–2 for HER and 234 mV at 20 mA cm–2 for OER, respectively. The NiCoSs shows the good bifunctional activities for overall water splitting and presents considerable stability for 24 hours. The good electrochemical activities of metal sulfides by using inorganic sodium sulfide can be attributed to the large exposed surface area and heterostructure compositions of Co9S8 and Ni3S2.

Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3-O-glucoside (M3G) and malvidin-3-O-galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress via suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.

Porphyrin nanostructures are widely used in the field of visible light catalysis due to their superior light absorption properties and good controllability in size, shape and function. In this paper, the development of various morphologies in three types of porphyrins with three different phenyl substituents (designated as H2TTP, H2TPP and H2TCPP, respectively) is demonstrated. The formation mechanism proposed was based on the evolution of morphology as functions of molecular structure and solvent mixture. These nano/micro assemblies are well characterized by SEM, IR, UV-vis, X-ray diffraction and photoelectric conversion. The photocatalytic oxidation reactions under visible light irradiation of 1,5-dihydroxynaphthalene (DHN) in water is utilized to evaluate the photoactivity of the as-prepared porphyrin assemblies. The photocatalytic results indicate that the obtained porphyrin assemblies exhibit enhanced visible-light photocatalytic activity. In addition, the photocatalyst is easy to separate and recover, and has good stability. The possible photocatalytic degradation mechanism of DHN by the porphyrins nanopolyhedron photocatalyst was also proposed.

Sepsis caused acute lung injury (ALI) is a kind of serious disease in critically ill patients with very high morbidity and mortality. Recently, it has been demonstrated that Golgi is involved in the process of oxidative stress. However, whether Golgi stress is associated with oxidative stress in septic induced acute lung injury has not been elucidated. In this research, we found that lipopolysaccharide (LPS) induced oxidative stress, apoptosis, inflammation and Golgi morphology changes in acute lung injury both in vivo and in vitro. The knockout of heme oxygenase-1(HO-1) aggravated oxidative stress, inflammation, apoptosis and reduced the expression of Golgi matrix protein 130 (GM130), mannosidase Ⅱ, Golgi-associated protein golgin A1 (Golgin 97), and increased the expression of Golgi phosphoprotein 3 (GOLPH3), which caused the fragmentation of Golgi. Furtherly, the activation of hypoxia inducible factor-1α (HIF-1α)/HO-1 pathway, attenuates Golgi stress and oxidative stress by increasing the levels of GM130, mannosidase Ⅱ, Golgin 97, and decreasing the expression of GOLPH3 both in vivo and in vitro. Therefore, the activation of HO-1 plays a crucial role in alleviating sepsis-induced acute lung injury by regulating Golgi stress, oxidative stress, which may provide a therapeutic target for the treatment of acute lung injury., Graphical abstract Image 1

Epilepsy is accompanied by abnormal neurotransmission, and microRNAs, as versatile players in the modulation of gene expression, are important in epilepsy pathology. Here, we found that miR-128 expression was elevated in the acute seizure phase and decreased during the recurrent seizure phase after status epilepticus in mice. Both SNAP-25 and SYT1 are regulated by miR-128 in vitro and in vivo. Overexpressing miR-128 in cultured neurons decreased neurotransmitter released by suppressing SNAP-25 and SYT1 expression. Anti-miR-128 injection before kainic acid (KA) injection increased the sensitivity of mice to KA-induced seizures, while overexpressing miR-128 at the latent and recurrent phases had a neuroprotective effect in KA-induced seizures. Our study shows for the first time that miR-128, a key regulator of neurotransmission, plays an important role in epilepsy pathology and that miR-128 might be a potential candidate molecular target for epilepsy therapy.

International audience; The genome of the hyperthermophilic and piezophilic euryarchaeaon Thermococcus barophilus Ch5 encodes three putative alcohol dehydrogenases (Tba ADHs). Herein, we characterized Tba ADH547 biochemically and probed its mechanism by mutational studies. Our data demonstrate that Tba ADH547 can oxidize ethanol and reduce acetaldehyde at high temperature with the same optimal temperature (75 o C) and exhibit similar thermostablilty for oxidization and reduction reactions. However, Tba ADH547 has different optimal pH for oxidation and reduction: 8.5 for oxidation and 7.0 for reduction. Tba ADH547 is dependent on a divalent ion for its oxidation activity, among which Mn 2+ is optimal. However, Tba ADH547 displays about 20% reduction activity without a divalent ion, and the maximal activity with Fe 2+. Furthermore, Tba ADH547 showcases a strong substrate preference for 1-butanol and 1-hexanol over ethanol and other alcohols. Similarly, Tba ADH547 prefers butylaldehyde to acetaldehyde as its reduction substrate. Mutational studies showed that the mutations of residues D195, H199, H262 and H234 to Ala result in the significant activity loss of Tba ADH547, suggesting that residues D195, H199, H262 and H234 are responsible for catalysis. Overall, Tba ADH547 is a thermoactive ADH with novel biochemical characteristics, thereby allowing this enzyme to be a potential biocatalyst.

An experimental study was carried out to investigate the combustion characteristics of plant-derived polyol liquor waste using thermogravimetric analyzer and vertical tube furnace tests. The research results showed that the waste liquor combustion reaction comprised four processes: evaporation, pyrolysis, combustion, and inorganic salt reaction, and that a wave peak exists for each process. The pyrolysis process, which is the most violent reaction, exhibited the maximum peak weight-loss rate and weight-loss ratio and had the lowest activation energy and frequency factor. The peak weight-loss rate of inorganic salt reaction process was less than that during the combustion process, but sodium alkali has catalytic effect at high temperature, which makes the activation energy and the frequency factor of inorganic salt reaction process less than that of the combustion process. The ignition temperature of the waste liquor in the vertical tube furnace was lower than the temperature in the thermogravimetric analyzer. The ignition temperature of pyrolysis volatiles measured in a vertical tube furnace was less than 700 °C but the ignition temperature of carbon combustion as measured with TG – DTG was 718 °C. When the temperature inside vertical tube furnace was higher than 800 °C, the waste liquor combustion process becomes almost instantaneous (about 8 s) and is violent, which produces more residual carbon content in the combustion products as a longer holding time is necessary to ensure that the reaction is completed.

Ligand-modified nanoparticles (NPs) have been widely used in oral drug delivery systems to promote endocytosis on intestinal epithelia. However, their transcytosis across the intestinal epithelia is still limited. Except for complex intracellular trafficking, recycling again from the apical sides into the intestinal lumen of the endocytosed NPs cannot be ignored. In this study, we modified NP surfaces with angiopep-2 (ANG) that targeted the low-density lipoprotein receptor-related protein 1 (LRP-1) expressed on the intestine to increase both the apical endocytosis and basolateral transcytosis of NPs. Notably, our finding revealed that ANG NPs could increase the apical expression and further basolateral redistribution of LRP-1 on Caco-2 cells, thus generating an apical-to-basolateral absorption pattern. Because of the enhanced transcytosis, insulin loaded ANG NPs possessed much stronger absorption efficiency and induced maximal blood glucose reduction to 61.46% in diabetic rats. Self-regulating the distribution of receptors on polarized intestine cells to promote basolateral transcytosis will provide promising insights for the rational design of oral delivery systems of protein/peptide drugs.

Background: Alcohol consumption is a potential risk factor for gastric cancer. However, findings from cohort studies that examined the relationship between alcohol consumption and gastric cancer risk among Japanese population are not conclusive. Methods: A total of 54,682 Japanese men and women participating in the Japan Collaborative Cohort study completed a questionnaire, including alcohol consumption information. The Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After a median 13.4-year follow-up, we documented 801 men and 466 women incident cases of gastric cancer. Alcohol consumption was associated with increased risk of gastric cancer among men (HRs in ex-drinkers and current alcohol consumption of = 69 g/d categories versus never drinkers were 1.82; 95% CI. 1.38-2.42. 1.41; 95% CI, 1.10-1.80, 1.47; 95% CI, 1.17-1.85, 1.88; 95% CI, 1.48-2.38, and 1.85; 95% CI, 1.35-2.53, respectively, and that for 10g increment of alcohol consumption after excluding ex-drinkers was 1.07; 95% CI, 1.04-1.10). The association in men was observed for cardia and non-cardia gastric cancer (HRs in the highest alcohol consumption category versus never drinkers were 9.96; 95% CI, 2.22-44.67 for cardia cancer and 2.40: 95% CI, 1.64-3.52 for non-cardia cancer). However, no such trend was observed in women. Conclusions: Alcohol consumption is associated with increased risk of gastric cancer among Japanese men, regardless of anatomical subsite of the cancer.

Direct functionalization of a C-H bond at either the meta or para position by only changing the catalyst system poses a significant challenge. We herein report the [Fe(TPP)Cl]-enabled, selective, C-H difluoromethylation of arenes using BrCF2CO2Et as the difluoromethylation source, which successfully altered the selectivity from the meta to the para position. A preliminary mechanistic study revealed the iron porphyrin complex not only activated the aromatic ring but also induced para selectivity due to the influence of ligand sterics.

Extractions from Phaeodactylum tricornutum have been widely studied and evaluated to various biological effects. The aim of this study was to investigate the promotional effect of P. tricornutum extract (PTE) on the ERK1/2 signaling pathway involved in hair follicle cell proliferation. In order to illuminate the enhancement of PTE on hair growth by promoting proliferation of hair follicle cells, the activities of human hair follicle outer root sheath cell (HFORSC), human hair follicle germinal matrix cells (HFGMC), and hair epithelial melanocytes (HEM) were observed under PET treatment. Levels of keratins, PKCζ, ERK1/2, and p38 MAPK in hair follicle cells were determined by Western blotting to illustrate the mechanisms of PTE effects on hair growth. Analyzed by GC-MS, the main polyunsaturated fatty acids which were 9.43% of total fatty acids in PTE were linolenic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid. Melanin content and tyrosinase activity in HEM were measured. The results showed that PTE exhibited remarkable enhancement on cell proliferation. Melanin production was inhibited by PTE treatment, while keratin-14, keratin-15, and keratin-17 levels on hair follicle cells were elevated at different concentrations. The promotions of ERK1/2 and p38 MAPK levels indicated that the ERK1/2 signaling pathway is involved in the proliferation of hair follicle cells. These results are the evidence that PTE potentially deserves further study as a new natural candidate for hair care applications.

Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl4) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of Lactobacillus, Bacteroides, and Akkermansia and decreased the relative abundance of Ralstonia, Alloprevotella, and Lachnoclostridium. However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.

Ethyl carbamate (EC) is a carcinogen toxicant, commonly found in fermented foods and beverages. The carcinogenic and toxic possibility of EC is thought to be related to its metabolite vinyl carbamate (VC). However, we found interesting mechanisms underlying VC-induced toxicity in this study, which were greatly different from EC. We first conducted a simple synthesis procedure for VC and found that VC possessed higher toxicity but failed to regulate levels of reactive oxygen species, glutathione, and autophagy. Notably, VC treatment resulted in upregulation of lysosomal pH, which was responsible for its cytotoxicity. Cyclic adenosine monophosphate (cAMP) pretreatment could enhance restoration of lysosomal acidity and ameliorate VC-induced damage. Inhibition of protein kinase A and cystic fibrosis transmembrane conductance regulator can block cAMP-induced cytoprotection. Together, our results provided the evidence for novel mechanisms of toxicity and possible protection method under VC exposure, which might give new perspectives on the study of EC-induced toxicity.

Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hidden) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/μL) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 levels could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.

Treatments for lesions in central nervous system (CNS) are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years. Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions, which requires an accurate recapitulation of the complex microenvironment of human brain in vitro. Here, a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid (HA) and normal glial cells (HEBs) is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin (GA) within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models. The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.

Using Calotropis gigantea fiber (CGF) as the bio-template, the magnetic carbonized fiber (MC-CGF) was successfully prepared by anchoring Fe3O4 onto CGF surface via pyrolysis, and well characterized by means of instrumental analysis. Subsequently, MC-CGF was used as the adsorbent to remove perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from water. The adsorption equilibrium of PFOA and PFOS on MC-CGF could be achieved within 1 h and 2 h, with maximum adsorption capacity of ~ 200 mg/g for them at pH 3.0. Coexisting ions (Na+, Mg2+, Fe3+) promoted the adsorption efficiency of MC-CGF to PFOA/PFOS, in particular for multivalent metal cations. During the adsorption process, hydrophobic interaction was principally involved, and was considered to be the driving force for fast removal of perfluoroalkyl pollutants. Such a hydrophobic-driven interaction was further evidenced using other perfluoroalkyl pollutants with different C–F chain length and functional groups as the models. Finally, MC-CGF was easily regenerated and recycled many times, demonstrating its potential for removing perfluoroalkyl pollutants from water in the future.

Activation of the Wnt/β-catenin signaling pathway by the inhibition of glycogen synthase kinase-3 (GSK-3) will induce Tcf7l1 protein degradation to effectively promote embryonic stem cell (ESC) self-renewal. However, the exact mechanism remains unclear. Here, we found that inhibition of casein kinase 2 (Csnk2) by TBB or DMAT was sufficient to block the reduction of the Tcf7l1 protein induced by CHIR99021, a specific inhibitor of GSK-3. Similarly, downregulation of Csnk2 increased the Tcf7l1 level. In contrast, overexpression of Csnk2 significantly decreased Tcf7l1 protein stability in mouse ESCs. Notably, Csnk2α1 controls Tcf7l1 turnover to a greater degree than the other two isoforms of Csnk2, Csnk2α2 and Csnk2β, as Csnk2α1-overexpressing mouse ESCs exhibited the lowest level of Tcf7l1. Csnk2α1 interacted with and phosphorylated Tcf7l1. In addition, the association of Csnk2α1 and Tcf7l1 was enhanced by CHIR99021. Our study demonstrated, for the first time, that Csnk2 is involved in Tcf7l1 turnover mediated by the Wnt/β-catenin signaling pathway. These results expand our understanding of the function and circuit of Wnt/β-catenin signaling pathway in ESCs.

Tanshinol A, which is derived from a traditional Chinese herbal Radix Salviae Miltiorrhizae is indicative of a hypolipidemic candidate. Therefore, we aim to validate its hypolipidemic activity of tanshinol A and explore its mechanism in triton-1339W-induced hyperlipidemic mice model, which possess multiply pathogenesis for endogenous lipid metabolism disorder. Experimental hyperlipidemia mice are treated with or without tanshinol A (i.g. 40, 20, 10 mg/kg), and blood and liver tissue were collected for validating its hypolipidemic and hepatic protective effect, and hepatic mRNA expression profile, which was associated with lipid metabolism dysfunction and liver injury, was detected by RT-qPCR. As results show, triton-1339W-induced abnormal of serum TC, TAG, HDL-C, LDL-C, SOD, MDA, GOT, and GPT is remarkably attenuated by tanshinol A. In pathological experiment, triton-1339W-induced hepatocellular ballooning degeneration, irregular central vein congestion, and inflammation infiltration are alleviated by tanshinol A. Correspondingly, hepatic mRNA expression of Atf4, Fgf21, Vldlr, Nqo1, Pdk4, and Angptl4, which are genes regulating lipemic-oxidative injury, are significantly increased by tanshinol A by 2~6 fold. Abcg5, Cd36, and Apob, which are responsible for cholesterol metabolism, are mildly upregulated. Noticeably, triton-1339W-suppressed expressions of Ptgs2/Il10, which are genes responsible for acute inflammation resolution in liver injury, are remarkably increased by tanshinol A. Conclusively, tanshinol A exerted hypolipidemic effect and hepatoprotective effect through restoring triton-1339W-suppressed mRNA expression, which may be involved in Atf4/Fgf21/Vldlr and Ptgs2/Il-10 signaling pathways.

Dietary advanced glycation end products (AGEs) are formed via the Maillard reaction in foods, especially in reheated foods, and can cause chronic diseases. In this study, a series of Maillard reaction-based time–temperature indicators (TTIs: TTI-1, TTI-2, and TTI-3) were developed with lysine and xylose for monitoring the dynamic formation of fluorescent AGEs in reheated foods. The discoloration kinetics of Maillard reaction-based TTIs and the dynamics of fluorescent AGE formation were explored. Formulas were derived to illustrate the relationship of the color change in the TTIs with time and temperature. The activation energies (Ea values) for generating the TTIs were 96.17, 87.98, and 83.55 kJ mol−1, respectively. TTI-1 was the optimal indicator for instant soy milk powder because it showed the lowest activation energy difference in this study. The results show that this series of Maillard reaction-based TTIs can be used to monitor the AGE contents in various reheated foods.

A dual-functional urea-linked conjugated porous polymer (UCPP) assembled by enol–imine with ordered unit arrays that act as potential anchoring sites in the networks was fabricated, and was further applied as a support for Ag nanoparticles by the coordinate interaction between them. The UCPP not only can well confine the Ag particle size and facilitate high dispersion, but also can afford special CO2-philic moieties to enhance the adsorption properties. The resulting Ag@UCPP as a heterogeneous catalyst exhibited excellent activity for the carboxylative cyclization of propargyl alcohols with CO2 under mild conditions, together with good recyclability, which is probably attributed to the synergistic effect of the UCPP on the adsorption and activation of CO2 and the immobilization of Ag nanoparticles. This work affords possible opportunities for the design and synthesis of a heterogeneous catalyst toward CO2 conversion.

By embedding regulated genetic circuits and cell-free systems onto a paper, the portable in vitro biosensing platform showed the possibility of detecting environmental pollutants, namely arsenic ions and bacterial quorum-sensing signal AHLs (N-acyl homoserine lactones). This platform has a great potential for practical environmental management and diagnosis.

Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

Embryonic stem cells (ESCs) are progenitor cells that retain the ability to differentiate into various cell types and are necessary for tissue repair. Improving cell culture conditions to maintain the pluripotency of ESCs in vitro is an urgent problem in the field of regenerative medicine. Here, we reveal that Spautin-1, a specific small-molecule inhibitor of ubiquitin-specific protease (USP) family members USP10 and USP13, promotes the maintenance of self-renewal and pluripotency of mouse ESCs in vitro. Functional studies reveal that only knockdown of USP13, but not USP10, is capable of mimicking the function of Spautin-1. Mechanistically, we demonstrate that USP13 physically interacts with, deubiquitinates, and stabilizes serine/threonine kinase Raf1 and thereby sustains Raf1 protein at the posttranslational level to activate the FGF/MEK/ERK prodifferentiation signaling pathway in naive mouse ESCs. In contrast, in primed mouse epiblast stem cells and human induced pluripotent stem cells, the addition of Spautin-1 had an inhibitory effect on Raf1 levels, but USP13 overexpression promoted self-renewal. The addition of an MEK inhibitor impaired the effect of USP13 upregulation in these cells. These findings provide new insights into the regulatory network of naive and primed pluripotency.

Intelligent polymer nanocapsules that can not only encapsulate substances efficiently but also release them in a controllable manner hold great potential in many applications. To date, although intensive efforts have been made to develop intelligent polymer nanocapsules, how to construct the well-defined core/shell structure with high stability via a straightforward method remains a considerable challenge. In this work, the target novel zwitterionic nanocapsules (ZNCs) with a stable hollow structure were synthesized by inverse reversible addition fragmentation transfer (RAFT) miniemulsion interfacial polymerization. The shell gradually grew from the water/oil interface due to the interfacial polymerization, accompanied by the cross-linking of the polyzwitterionic networks, where the core/shell structure could be well-tuned by adjusting the precursor compositions. The resultant ZNCs exhibited a salt-/thermo-induced swelling behavior through the phase transition of the external zwitterionic polymers. To further investigate the functions of ZNCs, different substances, such as methyl orange and bovine serum albumin (BSA), were encapsulated into the ZNCs with a high encapsulation efficiency of 89.3 and 93.6%, respectively. Interestingly, the loaded substances can be controllably released in aqueous solution triggered by salt or temperature variations, and such responsiveness also can be utilized to bounce off the bacteria adhered on target surfaces. We believe that these designed salt- and thermo-responsive intelligent polymer nanocapsules with well-defined core/shell structures and antifouling surfaces should be a promising platform for biomedical and saline related applications.

Cereal crops have starch in their endosperm, which has provided calories to humans and livestock since the dawn of civilization to the present day. Starch is one of the important biological factors which is contributing to the yield of cereal crops. Starch is synthesized by different enzymes, but starch structure and amount are mainly determined by the activities of starch synthase enzymes (SS) with the involvement of starch branching enzymes (SBEs) and debranching enzymes (DBEs). Six classes of SSs are found in Arabidopsis and are designated as soluble SSI-V, and non-soluble granule bound starch synthase (GBSS). Soluble SSs are important for starch yield considering their role in starch biosynthesis in cereal crops, and the activities of these enzymes determine the structure of starch and the physical properties of starch granules. One of the unique characteristics of starch structure is elongated glucan chains within amylopectin, which is by SSs through interactions with other starch biosynthetic enzymes (SBEs and DBEs). Additionally, soluble SSs also have conserved domains with phosphorylation sites that may be involved in regulating starch metabolism and formation of heteromeric SS complexes. This review presents an overview of soluble SSs in cereal crops and includes their functional and structural characteristics in relation to starch synthesis.

Different crystal planes of nanocrystalline often displayed diverse physical and chemical properties. In this paper, the effects of nano-ZnO with two kinds of crystal planes on crystallization, thermal stability and mechanical properties of PLLA were investigated. The results show that the (1010) planes with no-polar and low surface energy increased the chain mobility of PLLA chain, showed a plasticizing effect; the glass transition temperature, melt and cold crystallization temperature decreased by 12 °C, 10 °C and 12 °C, respectively. The size of spherulites increased and the number of spherulites decreased, the crystal form changed from mixed crystal form α, α′ to unique α crystal form. However, the (0002) planes with polar and high surface energy has highly nucleating effective for PLLA, the crystallization temperature increased to 106.41 °C, the cold crystallization peak disappear. The size of spherulites decreased and the number of spherulites increased. Moreover, the (0002) planes increases the elongation at break of PLLA to 20.34% but the (1010) planes reduces to 7.49%. Their thermo-gravimetric analysis results showed the similar trend. Our results indicate that the interface wettability and compatibility between crystal planes and PLLA, which was caused by the polarity and surface energy of (1010) or (0002) planes played key role in improving the performance of polymers.

Diabetes has become one of the three chronic non-communicable diseases threatening human health in the world, and the detection of glucose concentration is of great importance for the prevention and treatment of diabetes. The noninvasive detection of glucose in tears has attracted interest over the past several decades, however, time-consuming, expensive equipment, and specialist technicians make tear analysis still challenging. Here, flexible surface-enhanced Raman scattering (SERS) substrates composed of gold nanoparticles (AuNPs) and two-dimensional MXene Ti3C2TX nanosheets have been designed. The GMXeP (gold nanoparticles with MXene nanosheets loaded on paper) SERS substrates show good sensitivity, reproducibility, and stability, yielding an enhancement factor (EF) of 3.7 × 105 at the concentration of 10-9 M. The GMXeP SERS substrates are used to detect glucose of diabetic tears within a linear range of 1–50 μM, the lowest detection concentration is 0.39 μM and the significant correlation between tear glucose and blood glucose indicates that this method is suitable for sensitive and noninvasive detection of blood glucose.

A novel polysaccharide (CMP-2B) was purified from Centipeda minima by anion-exchange and gel-permeation chromatography. Structural characterization revealed that CMP-2B was a homogeneous heteropolysaccharide with an average molecular weight of 113.193 KDa. CMP-2B was made up of mannose, galacturonic acid, galactose and arabinose with a molar ratio of 0.27:0.12:0.42:0.17. The backbone chain of CMP-2B consisted of 3,6)-α-D-Manp-(1 and 4,6)-β-D-Galp-(1, and the branches were comprised of 4)-α-D-GalpA-(1, 6)-β-D-Galp-(1, T-α-L-Araf-(1 and 3)-α-L-Araf -(1. Besides, the results of antioxidant assays revealed that CMP-2B possessed signifcant free radical scavenging ability. Moreover, the results of hypoglycemic assays showed that CMP-2B displayed α-glucosidase inhibitory activities, and could significantly improve glucose consumption, glycogen synthesis and the activity of pyruvate kinase of insulin-resistance HepG2 cells. Overall, these results suggested that CMP-2B could be a new source for functional foods.

Recently, several reports have suggested that the growth and grain yield of wheat are significantly influenced by high atmospheric carbon dioxide concentration (CO2) because of it photosynthesis enhancing effects. Moreover, it has been proposed that plants with large carbon sink size will benefit more from CO2 enrichment than those with small carbon sink size. However, this hypothesis is yet to be test in winter wheat plant. Therefore, the aim of this study was to examine the effect of elevated CO2 (eCO2) conditions on the quantum efficiency of photosystem II (PSII) photochemistry in large ear-type (cv. Shanhan 8675; greater ear C sink strength) and small multiple ear-type (cv. Early premium; greater vegetative C source strength) winter wheat varieties. The experiment was conducted in a free air CO2 enrichment (FACE) facility, and three de-excitation pathways of the primary reaction of PSII of flag leaf at the anthesis stage were evaluated under two CO2 concentrations (ambient [CO2], ∼415 μmol⋅mol–1, elevated [CO2], ∼550 μmol⋅mol–1) using a non-destructive technique of modulated chlorophyll fluorescence. Additionally, the grain yield of the two varieties was determined at maturity. Although elevated CO2 increased the quantum efficiency of PSII photochemistry (ΦPSII) of Shanhan 8675 (SH8675) flag leaves at the anthesis stage, the grain number per ear and 1,000-kernel weight were not significantly affected. In contrast, the ΦPSII of early premium (ZYM) flag leaves was significantly lower than that of SH8675 flag leaves at the anthesis stage, which was caused by an increase in the regulatory non-photochemical energy dissipation quantum (ΦNPQ) of PSII, suggesting that light energy absorbed by PSII in ZYM flag leaf was largely dissipated as thermal energy. The findings of our study showed that although SH8675 flag leaves exhibited higher C sink strength and quantum efficiency of PSII photochemistry at the anthesis stage, these factors alone do not ensure improved grain yield under eCO2 conditions.

This work investigated the influence of enzymatic tenderization on digestibility changes of beef semimembranosus proteins using peptidomics methods. Hydrolysis by proteinase K and bromelain elevated the average bitterness index of identified peptides by generating high

Patients with bladder cancer (BCa) with clinical lymph node (LN) metastasis have an extremely poor prognosis. VEGF-C has been demonstrated to play vital roles in LN metastasis in BCa. However, approximately 20% of BCa with LN metastasis exhibits low VEGF-C expression, suggesting a VEGF-C-independent mechanism for LN metastasis of BCa. Herein, we demonstrate that BCa cell-secreted exosome-mediated lymphangiogenesis promoted LN metastasis in BCa in a VEGF-C-independent manner. We identified an exosomal long noncoding RNA (lncRNA), termed lymph node metastasis-associated transcript 2 (LNMAT2), that stimulated human lymphatic endothelial cell (HLEC) tube formation and migration in vitro and enhanced tumor lymphangiogenesis and LN metastasis in vivo. Mechanistically, LNMAT2 was loaded to BCa cell-secreted exosomes by directly interacting with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1). Subsequently, exosomal LNMAT2 was internalized by HLECs and epigenetically upregulated prospero homeobox 1 (PROX1) expression by recruitment of hnRNPA2B1 and increasing the H3K4 trimethylation level in the PROX1 promoter, ultimately resulting in lymphangiogenesis and lymphatic metastasis. Therefore, our findings highlight a VEGF-C-independent mechanism of exosomal lncRNA-mediated LN metastasis and identify LNMAT2 as a therapeutic target for LN metastasis in BCa.