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Fibroblast growth factor-18 (FGF18) has diverse organ development and damage repair roles. However, its role in cardiac homeostasis following hypertrophic stimulation remains unknown. Here we investigate the regulation and function of the FGF18 in pressure overload (PO)-induced pathological cardiac hypertrophy. FGF18 heterozygous (Fgf18+/−) and inducible cardiomyocyte-specific FGF18 knockout (Fgf18-CKO) male mice exposed to transverse aortic constriction (TAC) demonstrate exacerbated pathological cardiac hypertrophy with increased oxidative stress, cardiomyocyte death, fibrosis, and dysfunction. In contrast, cardiac-specific overexpression of FGF18 alleviates hypertrophy, decreased oxidative stress, attenuates cardiomyocyte apoptosis, and ameliorates fibrosis and cardiac function. Tyrosine-protein kinase FYN (FYN), the downstream factor of FGF18, was identified by bioinformatics analysis, LC-MS/MS and experiment validation. Mechanistic studies indicate that FGF18/FGFR3 promote FYN activity and expression and negatively regulate NADPH oxidase 4 (NOX4), thereby inhibiting reactive oxygen species (ROS) generation and alleviating pathological cardiac hypertrophy. This study uncovered the previously unknown cardioprotective effect of FGF18 mediated by the maintenance of redox homeostasis through the FYN/NOX4 signaling axis in male mice, suggesting a promising therapeutic target for the treatment of cardiac hypertrophy.

The nano-sperm is developed for ultrafast delivery of antisense DNA into cancer cells. Carried by silver nanoclusters at the “head”, antisense DNA as the cargo at the “tail” can be transported into cells rapidly, thereby inhibiting cell proliferation.

Lysinibacillus sp. is a spore-forming gram-positive bacterium showing excellent adaptive capacity to environment, convenience to storage and antimicrobial properties. Thus, it has appeared a huge potential as probiotics in application, but related studies remain limited. This study was conducted to determine the effects of supplementary Lysinibacillus (L.) macroides 38328 in drinking water on antioxidant capacity and avian influenza virus vaccine immune response of laying hens. Hereon, layers were fed with drinking water with or without supplementary L. macroides 38328 at the dose of 7×109 colony-forming units per milliliter (CFU/mL). The results showed that supplementation with L. macroides 38328 significantly improved the layers’ productive performance while enhancing their antioxidant capacity and immunity. According to the testing results, the rise of serum T-AOC and the downtrend of serum MDA were significant (P L. macroides 38328 had positive effects on layers’ heath condition and productivity, indicating great applied potential as a new probiotics strain.

There is an increasing interest in the use of spore-forming Bacillus spp. as probiotic ingredients on the market. However, probiotics Bacillus species are insufficient, and more safe Bacillus species were required. In the study, traditional fermented foods and soil samples were collected from all over the country in China, and 506 Bacillus were selected from 109 samples. Using the optimized procedure, we screened 9 strains, which successfully passed the acid, alkali, bile salt and trypsin resistance test. Drug sensitivity test results showed that three Bacillus out of the 9 isolates exhibited antibiotic sensitivity to more than 29 antibiotics. The 3 strains sensitive to antibiotics were identified by 16S ribosomal RNA, recA and gyrB gene analysis, two isolates (38327 and 38328) belong to the specie Lysinibacillus capsici and one isolate (37326) belong to Bacillus halotolerans. Moreover, the 3 strains were confirmed safe through animal experiments. Finally, L. capsici 38327 and 38328 showed the protection in Salmonella typhimurium infection mouse model, which manifested in slowing down weight loss, reducing bacterial load, improving antioxidant capacity. Altogether, our data demonstrate selected L. capsici strains can be used novel probiotics for intestinal health.

Acute myocardial infarction (MI) triggers oxidative stress, which worsen cardiac function, eventually leads to remodeling and heart failure. Unfortunately, effective therapeutic approaches are lacking. Fibroblast growth factor 7 (FGF7) is proved with respect to its proliferative effects and high expression level during embryonic heart development. However, the regulatory role of FGF7 in cardiovascular disease, especially MI, remains unclear. FGF7 expression was significantly decreased in a mouse model at 7 days after MI. Further experiments suggested that FGF7 alleviated MI-induced cell apoptosis and improved cardiac function. Mechanistic studies revealed that FGF7 attenuated MI by inhibiting oxidative stress. Overexpression of FGF7 actives nuclear factor erythroid 2-related factor 2 (Nrf2) and scavenging of reactive oxygen species (ROS), and thereby improved oxidative stress, mainly controlled by the phosphatidylinositol-3-kinase α (PI3Kα)/AKT signaling pathway. The effects of FGF7 were partly abrogated in Nrf2 deficiency mice. In addition, overexpression of FGF7 promoted hexokinase2 (HXK2) and mitochondrial membrane translocation and suppressed mitochondrial superoxide production to decrease oxidative stress. The role of HXK2 in FGF7-mediated improvement of mitochondrial superoxide production and protection against MI was verified using a HXK2 inhibitor (3-BrPA) and a HXKII VDAC binding domain (HXK2VBD) peptide, which competitively inhibits localization of HXK2 on mitochondria. Furthermore, inhibition of PI3Kα/AKT signaling abolished regulation of Nrf2 and HXK2 by FGF7 upon MI. Together, these results indicate that the cardio protection of FGF7 under MI injury is mostly attributable to its role in maintaining redox homeostasis via Nrf2 and HXK2, which is mediated by PI3Kα/AKT signaling.

In this work, an ultrasensitive immunosensor for amperometric determination of alpha-fetoprotein (AFP) was developed utilizing Ag and Cu nanoparticles on polydopamine (PDA) functionalized cellulose nanofibrils (CNFs) composite (CNFs/PDA/Cu-Ag) as signal amplifier. PDA was first prepared by self-polymerizing of dopamine, and then was adsorbed on CNFs. The obtained CNFs/PDA was applied as substrate to electrolessly deposit Cu-Ag nanoparticles, using NaBH

Disease-related biomarkers may serve as indicators of human disease. The clinical diagnosis of diseases may largely benefit from timely and accurate detection of biomarkers, which has been the subject of extensive investigations. Due to the specificity of antibody and antigen recognition, electrochemical immunosensors can accurately detect multiple disease biomarkers, including proteins, antigens, and enzymes. This review deals with the fundamentals and types of electrochemical immunosensors. The electrochemical immunosensors are developed using three different catalysts: redox couples, typical biological enzymes, and nanomimetic enzymes. This review also focuses on the applications of those immunosensors in the detection of cancer, Alzheimer’s disease, novel coronavirus pneumonia and other diseases. Finally, the future trends in electrochemical immunosensors are addressed in terms of achieving lower detection limits, improving electrode modification capabilities and developing composite functional materials.

Carbon dots (CDs) are widely used in the detection of foodborne contaminants because of their biocompatibility, photoluminescence stability, and ease of chemical modification. In order to solve the interference problem of complexity in food matrices, the development of ratiometric fluorescence sensors shows great prospects. In this review, the progress of ratiometric fluorescence sensors based on CDs in foodborne contaminant detection in recent years will be summarized, focusing on the functionalized modification of CDs, the fluorescence sensing mechanism, the types of ratiometric fluorescence sensors, and the application of portable devices. In addition, the outlook on the development of the field will be presented, with the development of smartphone applications and related software helping to better enable the on-site detection of foodborne contaminants to ensure food safety and human health.

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC

Cardiac hypertrophy occurs initially in response to an increased cardiac load as a compensatory mechanism to maintain cardiac output. However, sustained pathological hypertrophy can develop into heart failure and cause sudden death. Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family, which involved in apoptosis, aging, inflammation, and autophagy. The precise function of FGF20 in pathological cardiac hypertrophy is unclear. In this study, we demonstrated that FGF20 was significantly decreased in response to hypertrophic stimulation. In contrast, overexpression of FGF20 protected against pressure overload-induced cardiac hypertrophy. Mechanistically, we found that FGF20 upregulates SIRT1 expression, causing deacetylation of FOXO1; this effect promotes the transcription of downstream antioxidant genes, thus inhibits oxidative stress. In content, the anti-hypertrophic effect of FGF20 was largely counteracted in SIRT1-knockout mice, accompanied by an increase in oxidative stress. In summary, our findings reveal a previously unknown protective effect of FGF20 on pathological cardiac hypertrophy by reducing oxidative stress through activation of the SIRT1 signaling pathway. FGF20 is a potential novel molecular target for preventing and treating pressure overload-induced myocardial injury.

Summary Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma‐carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non‐invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.

Novel bactericidal materials, polycation-based N-halamine functionalized nanodiamonds (PCN-NDs), were fabricated by coating of nanodiamonds (NDs) with quaternarized N-halamine polymers via a facile approach. Chemical modification of the particles was confirmed by FTIR, XPS and TGA. The particle diameters and dispersity of the functionalized NDs were investigated by TEM and DLS measurements. It was found that ND tight core aggregates could be broken into tiny nanoparticles with 40-50 nm through functionalization procedure, which resulted in stable colloidal dispersion solution over one month. The antibacterial tests showed that the PCN-NDs exhibited enhanced antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) compared with their bulk counterparts. The minimum inhibitory concentration values of the as-prepared PCN-NDs are 62.5 μg/mL for both E. coli and S. aureus, even PCN-NDs eliminated nearly 100% of E. coil and S. aureus (107-108 CFU/mg nanoparticles) within 15 min. Furthermore, the as-prepared antimicrobial PCN-NDs exhibited good storage stability and regenerability.

Background/Aims: Cholangiocarcinoma (CCA) is a malignant tumor that is resistant to chemotherapy, so new therapeutic agents are needed. Allicin which is rapidly converted from allin by allinase, is one of the most biologically active compounds in freshly crushed garlic and has been shown to have strong anti-tumor effects. Our aim was to explore the molecular mechanism by which allicin affects the cell proliferation and invasion of CCA. Methods: Cell viability and apoptosis were measured using the CCK-8 assay, colony formation assay, and flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell assays, respectively. The expression of several proteins involved in cell apoptosis and invasion were assessed by Western blot. The activation of STAT3 signaling was detected by Western blot and immunofluorescence staining. The involvement of SHP-1 was determined using small interfering RNA (siRNA). Moreover, a nude mouse model of human CCA was established to assess the anti-tumor effects of allicin in vivo. Results: Allicin significantly suppressed CCA cell proliferation by activating the caspase cascade, inducing apoptosis, and reducing the expression of proteins downstream of STAT3, such as B-cell lymphoma 2 (Bcl-2), while upregulating Bcl-2-associated X (Bax) protein. In addition, allicin inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. Moreover, the protein expression of MMP-2 and MMP-9 was significantly downregulated in CCA cells treated with allicin compared with CCA cells treated with control. Mechanistic investigations indicated that allicin upregulated SHP-1 expression in CCA, and pervanadate treatment reversed the allicin-induced downregulation of STAT3. Moreover, suppression of SHP-1 by siRNA overturned the effect of allicin on the induction of SHP-1 and inhibition of STAT3 activation. Additionally, treatment with allicin attenuated tumor growth in the nude mouse model of CCA. Conclusions: Our findings suggest that allicin suppresses cell proliferation and invasion via STAT3 signaling and may be a potential therapeutic agent for CCA.

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as disease triggers. Many studies have indicated that alterations in the gut microbiota are important environmental factors in the development of inflammatory and autoimmune diseases. A comparative analysis was systematically performed of the gut microbiota in HT patients and healthy controls.First, a cross-sectional study of 28 HT patients and 16 matched healthy controls was conducted. Fecal samples were collected, and microbiota were analyzed using 16S ribosomal RNA gene sequencing. Second, an independent cohort of 22 HT patients and 11 healthy controls was used to evaluate the diagnostic potential of the selected biomarkers.Similar levels of bacterial richness and diversity were found in the gut microbiota of HT patients and healthy controls (p = 0.11). A detailed fecal microbiota Mann-Whitney U-test (Q value0.05) revealed that the abundance levels of Blautia, Roseburia, Ruminococcus_torques_group, Romboutsia, Dorea, Fusicatenibacter, and Eubacterium_hallii_group genera were increased in HT patients, whereas the abundance levels of Fecalibacterium, Bacteroides, Prevotella_9, and Lachnoclostridium genera were decreased. A correlation matrix based on the Spearman correlation distance confirmed correlations among seven clinical parameters. Additionally, the linear discriminant analysis effect size method showed significant differences in 27 genera between the two groups that were strongly correlated with clinical parameters. The linear discriminant analysis value was used to select the first 10 species from the 27 different genera as biomarkers, achieving area under the curve values of 0.91 and 0.88 for exploration and validation data, respectively.Characterization of the gut microbiota in HT patients confirmed that HT patients have altered gut microbiota and that gut microbiota are correlated with clinical parameters, suggesting that microbiome composition data could be used for disease diagnosis. Further investigation is required to understand better the role of the gut microbiota in the pathogenesis of HT.

Breast cancer is a serious threat to the health of women all over the world. The precise diagnosis and treatment of breast cancer are of great importance to control the development of breast cancer as well as to improve survival rates of the patients. Nowadays, polypeptides are widely applied in breast cancer-related research, benefiting from lower immunogenicity, better biodegradability, higher penetration, and easier synthesis and modification. In this review, we have summarized recent applications of functional polypeptides in the detection and imaging of breast cancer, in which polypeptides work not only as a recognition element and signal source for detecting and imaging breast tumours, but also a building block and a therapeutic drug to assist image-guided treatment of breast cancer.

The delivery of mRNA to manipulate protein expression has attracted widespread attention, since that mRNA overcomes the problem of infection and mutation risks in transgenes and can work as drugs for the treatment of diseases. Although there are currently some vehicles that deliver mRNA into cells, they have not yet reached a good balance in terms of expression efficiency and biocompatibility. Here, a DNA nano-hydrogel system for mRNA delivery is developed. The nano-hydrogel is all composed of DNA except the target mRNA, so it has superior biocompatibility compared with those chemical vehicles. In parallel, the nano-hydrogel can be compacted into a nanosphere under the crosslinking by well-designed "X"-shaped DNA scaffolds and DNA linkers, facilitating the delivery into cells through endocytosis. In addition, smart intracellular release of the mRNA is achieved by incorporating a pH-responsive i-motif structure into the nano-hydrogel. Thus, taking the efficient delivery and release together, mRNA can be translated into the corresponding protein with a high efficiency, which is comparable to that of the commercial liposome but with a much better biocompatibility. Due to the excellent biocompatibility and efficiency, this nano-hydrogel system is expected to become a competitive alternative for delivering functional mRNA in vivo.

An antibacterial and biodegradable composite hydrogel dressing integrated with microspheres is developed for drug delivery and wound healing. The mechanism of gelation is attributed to the Schiff-base reaction between aldehyde and amino groups of oxidized alginate (OAlg) and carboxymethyl chitosan (CMCS). To enhance antibacterial and mechanical properties, tetracycline hydrochloride (TH) loaded gelatin microspheres (GMs) were fabricated by an emulsion cross-linking method, followed by integrating into the OAlg-CMCS hydrogel to produce a composite gel dressing. In vitro gelation time, swelling, degradation, compressive modulus and rheological properties of the gel dressing were investigated as the function of microsphere ratios. With increasing ratios of microspheres from 10 to 40mg/mL, the composite dressing manifested shorter gelation time and lower swelling ratios, as well as higher mechanical strength. Comparing to other formulations, the gel dressing with 30mg/mL microspheres showed more suitable stabilities and mechanical properties for wound healing. Also, in vitro drug release results showed that the loaded TH could be sustained release from the composite gel dressing by contrast with pure hydrogels and microspheres. Furthermore, powerful bacteria growth inhibition effects against Escherichia coli and Staphylococcus aureus suggested that the composite gel dressing, especially the one with 30mg/mL GMs containing TH, has a promising future in treatment of bacterial infection.

In this work, we propose a novel concept and a proof-of-concept strategy for the fabrication of a pH-based immunoassay platform with a certain degree of universality and scalability to make it adaptable for different application scenarios. The immunoreactions for the target detection are converted to pH changes through an engineered and optimized isothermal nucleic acid amplification, named exponential amplification reaction (EXPAR). Thus, a variety of well-developed methods for pH analysis, e.g. pH indicators, pH-strips and pH meters, can be applied for immunoassay directly. Here, we show that this proof-of-concept strategy is applicable for both macromolecular and micromolecular antigens by adopting human platelet-derived growth factor-BB (PDGF-BB) and chloramphenicol (CAP) as the model targets, respectively. The detection can be achieved using a colorimetric pH indicator after a 15 min reaction of the immuno-triggered isothermal nucleic acid amplification. In addition, compared with the traditional enzyme-linked immunosorbent assay (ELISA), the performance of our strategy, especially the detection limits, is improved to varying degrees for different targets, making the strategy a promising alternative for diverse application scenarios of immunoassay.

As a bifunctional enzyme, T4 polynucleotide kinase phosphatase (T4 PNKP) catalyzes the phosphorylation of 5′-hydroxyl, and also removes the terminal 3′-phosphate group. This is closely related to the restructuring, replication, and damage repair of nucleic acid. In this paper, we describe a new method for the sensitive detection of T4 PNKP activity based on the isothermal EXPonential amplification reaction (EXPAR). T4 PNKP can be linearly assayed in the range from 0.001 to 0.01 U mL−1 with a detection limit of 7.9 × 10−4 U mL−1. Moreover, the method exhibits high specificity and sensitivity and can be applied in the enzyme analysis of complex serum samples. In view of its simplicity and moderate experimental conditions, the method may suitable for use in a commercial kit for the analysis of T4 PNKP activity.

In this work, a cationic polymer, N-alkylated poly (4-vinylpyridine) was applied for the surface functionalization of nanodiamond (ND). The facile route not only settled the problems of agglomeration and poor dispersion stability of ND but also rendered the nanomaterial antibacterial property. Chemical modification of the particles was confirmed by FT-IR spectroscopy and 1HNMR, and the cationic polymer contents were determined by TGA studies. The particle diameters and dispersity of functionalized NDs were investigated by TEM and DLS measurements. It was found that extremely tight core aggregates (100–200 nm) were broken into tiny nanoparticles (20–30 nm) through functionalization with NPVP-propyl or NPVP-hexyl, which gave stable and homogeneous functionalized ND particles in colloidal solution. The antibacterial tests against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) showed that the cationic polymer-modified ND exerted certain antibacterial activity. The FE-SEM images indicated that NPVP-hexyl-ND particles were attached to the cell wall surface of E. coli, which subsequently led to the formation of nanoscale holes on cell membrane and eventually the serious destruction of cell wall. We suspected that the interaction of NPVP-hexyl-ND with bacteria may come from the electrostatic interactions, the intermolecular and surface forces between functionalized nanoparticles and cell membranes, which may damage the outer membranes of bacteria and result in cell death.

To meet the progressive requirements for bone regeneration purpose, injectable hydrogels have attracted increasing attention in tissue regeneration and local drug delivery applications. In this study, we report a facile method to prepare injectable and degradable polysaccharide-based hydrogels doubly integrated with hydroxyapatite (HAp) nanoparticles and calcium carbonate microspheres (CMs) under physiological condition. The mechanism of cross-linking is attributed to the Schiff-base reaction between amino and aldehyde groups of carboxymethyl chitosan (CMCS) and oxidized alginate (OAlg), respectively. Synchronously, tetracycline hydrochloride (TH) loaded CMs were fabricated by the precipitation reaction with an average diameter of 6.62 μm. To enhance bioactive and mechanical properties, nano-HAp and CMs containing TH were encapsulated into the polysaccharide-based hydrogel to form injectable gel scaffolds for imitation of bone niche. The gelation time, morphology, mechanical properties, swelling ratio and in vitro degradation of the gel scaffolds could be controlled by varying HAp and CMs contents. Moreover, the composite gel scaffolds had good sustained drug release and antibacterial properties, as confirmed by drugs release calculation and antibacterial evaluation. In addition, the gel scaffolds were found to be self-healing due to dynamic equilibrium of the Schiff-base linkages. These results suggested that the prepared composite gel scaffolds hold great potential for drug delivery and regeneration of irregular bone defects.

Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child–Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child–Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(>F) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child–Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI (r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway “bacterial invasion of epithelial cells” in patients, was highly negatively correlated with SBT (r = -0.57, p < 0.01). The severity of microbiota dysbiosis in LC patients depends on SBT rather than Child–Pugh score. SBT per se might be significantly related to the gut microbiota abnormalities observed in patients with LC.

Background: Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with gut microbiota. However, little is known regarding the gut microbiota after surgery treatment. Methods: This study used 16S rRNA sequencing to evaluate the gut microbiota difference of individuals with colorcetal adenoma, CRC, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signatures abundance. Findings: The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, which revealed impressive shifts in the gut microbiota before or during the development of CRC. Significant differences were observed in the gut microbiota of postoperative patients compared with CRC patients. Furthermore, we subdivided CRC postoperative patients into those with or without newly developed adenoma according to their colonoscopy findings. The gut microbiota of newly developed adenoma patients not only showed significant differences compared with clean intestine patients, but also more comparable to the gut microbiota of carcinoma patients than to healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to the prognosis of colorectal cancer. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.84. Interpretation: Therefore, with a better understanding of the alteration of the gut microbiota after surgery treatment for CRC patients, the microbiota may be used as non-invasive biomarkers for the diagnosis of newly developed adenomas which can even help to prevent cancer recurrence in postoperative patients. Clinical Trial Number: This study was registered at ClinicalTrials.gov and began on May 1, 2016 (NCT03385213). Funding Statement: This work was supported by the National Natural Science Foundation of China [81672351], the department of Education of Heilongjiang Province [1252HQ017], and the First Affiliated Hospital of Harbin Medical University [2012LX001]. All the funding from Yunwei Wei Ph.D. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The clinical trial was approved by the Research Ethics Committee of the First Affiliated Hospital of Harbin Medical University (IRB-AF/SC-08/05.0). The studies were strictly performed according to international guidelines regarding the conduct of clinical trials, and each patient provided written informed consent.

Chimeric antigen receptor-modified T cell (CART) therapy has been demonstrated to have significant effect on hematologic tumor in patients. However, many persistent obstacles and challenges still limit the application. It is known that CD8 T cells are a key component of antitumor immunity. An avasimibe-induced inhibition of cholesterol esterification has been shown to improve the antitumor response of CD8 T cells in mice. In this study, using human CD19-directed CART cells as effector cells and CD19-overexpressing K562 cells as target cells, we detected whether cholesterol acyltransferase inhibition by avasimibe can enhance the antitumor effect of human CART cells. After avasimibe treatment, the infection rate was dropped by up to 50% (P

This study aimed at investigating the interaction of V 2 O 5 species with TiO 2 and Al 2 O 3 supports to understand the effect of supports on SCR reaction. Analysis by XRD, BET, UV–vis, and DFT theoretical calculations, XPS, EPR and in situ DRIFT showed that the two kinds of supports could interact with V 2 O 5 . The interaction of electron excitation and charge transfer of supports to V 2 O 5 species was important to the formation of the reduced V 2 O 5 . These aspects increased the formation of superoxide ions that could improve the NO oxidation over V 2 O 5 /TiO 2 . It was responsible for the higher SCR catalytic activity of V 2 O 5 /TiO 2 than V 2 O 5 /Al 2 O 3 .

BACKGROUND Cadmium (Cd) is one of the most poisonous pollutants, and Cd pollution has become the limiting factor of rice production and quality improvement. Therefore it is of significant importance to monitor Cd toxicity by the detection of Cd contamination in rice with biomarkers. In the present study, sequence-related amplified polymorphism (SRAP) and physiological and biochemical methods were applied to determine the toxicological effects of Cd stress on rice. RESULTS With increasing Cd concentration and duration, the content of chlorophyll in the two rice varieties W7 and M63 decreased and that of malondialdehyde increased. This tendency was more apparent in M63. The antioxidant enzymes superoxide dismutase and peroxidase both increased significantly compared with controls. SRAP polymerase chain reaction results indicated significant differences between Cd treatments and controls in terms of SRAP profile, as well as genotypic differences. The genomic template stability (GTS) decreased with increasing Cd concentration and duration. Under the same treatment conditions, the GTS of W7 was higher than that of M63. Comparison analysis revealed that the changes in physiological and biochemical parameters of rice seedlings under Cd stress had a good correlation with the changes in SRAP profile. Furthermore, the changes in SRAP profile showed enhanced sensitivity in the roots of rice seedlings. CONCLUSION The SRAP profile and physiological and biochemical parameters could act as appropriate biomarkers for the measurement of Cd contamination during rice production. © 2014 Society of Chemical Industry

Nanostructured biopolymer hydrogels have great potential in the field of drug delivery and regenerative medicine. In this work, a nano-fibrous (NF) biopolymer hydrogel was developed for cell growth factors (GFs) delivery and in vitro osteogenesis. The nano-fibrous hydrogel was produced via biological conjugation of streptavidin functionalized hyaluronic acid (HA-Streptavidin) and biotin terminated star-shaped poly(ethylene glycol) (PEG-Biotin). In the present work, in vitro gelation, mechanical properties, degradation and equilibrium swelling of the NF hydrogel were examined. The potential application of this NF gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. Osteoblasts seeded directly in NF gel scaffold containing cell growth factor, e.g. bone morphogenetic protein 2 (BMP-2), was to mimic the in vivo microenvironment in which cells interface biomaterials and interact with BMP-2. In combination with BMP-2, the NF hydrogel exhibited beneficial effects on osteoblast activity and differentiation, which suggested a promising future for local treatment of pathologies involving bone loss.

Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications.

Timely and accurate prediction of wheel skid is the precondition for effective antiskid control of high speed trains (HSTs) to ensure its safe operation. Since wheel skid is usually accompanied with significant change of the wheel speed or/and other related system states, the wheel skid identification can be considered as a classification problem where different states can be distinguished before and after wheel skid occurs. Motivated by this observation, the authors establish in this work a wheel skid prediction method by using the support vector machine (SVM) technique that has been proven effective for linear and nonlinear classification and prediction. It is shown that by modifying the bias parameter of the SVM classifier, the proposed method can predict the trend of wheel skid rapidly before wheel skid is upcoming, thus an active antiskid control can be activated in advance to avoid wheel skid. The effectiveness of the proposed strategy for skid prediction and antiskid control is theoretically analyzed and validated via numerical simulations.

Adhesion control is a key technology for preventing or reducing wheel slip/skid and improving reliability of traction/braking systems of railway vehicles. With the running speed and operation span of trains increasing, the issue of wheel-rail adhesion becomes rather complex, making traditional re-adhesion based adhesion control strategy inapplicable for HST. This work proposes a novel active adhesion control strategy using observer based robust approach. It is shown that the developed method is able to instantly prevent wheel skid and sufficiently utilize available adhesion coefficient as the actual adhesion coefficient suddenly decreases. Furthermore, in contrast to traditional adhesion control, detecting actual adhesion condition and measurement of vehicle speed are not needed with the proposed method. Both theoretical analysis and simulation study verify the effectiveness of the proposed strategy.