•Only one exopolysaccharide fraction was obtained by HPSEC.•Monosaccharide composition of EPS is simple which distinguishes with other L. plantarum EPS.•Sulfated EPS displayed stronger radicals ...scavenging activities than EPS.•Sulfated EPS could protect Caco-2 cells from damage induced by enterotoxin of Bacillus cereus.
An exopolysaccharide (EPS) from probiotics Lactobacillus plantarum ZDY2013 was purified to illustrate its molecular weight, monosaccharide composition and biological activities. The yield of EPS (429.4±30.3mg/L) was obtained with a purity of 96.06%. The EPS was characterized to have only one symmetrical sharp peak by high-performance size-exclusion chromatography and its molecular weight was 5.17×104Da. The GC analysis revealed that EPS only consisted of xylose and galactose, and the galactose possessed as high as 98.3% (w/w) of the total monosaccharides. By sulfonation, a sulfated EPS was successfully synthesized with the degree of substitution (DS) of 0.29, which was confirmed using FT-IR spectroscopy. Both EPS and sulfated EPS showed radical scavenging activities, and the antioxidant activities increased after sulfonation. In addition, sulfated EPS was more effective in counteracting the cytotoxicity induced by B. cereus enterotoxins on Caco-2 cells when compared with EPS. In summary, sulfonation is a feasible strategy for improving the biological activities of EPS from L. plantarum ZDY203.
Owning to the misuse of the antibiotics in animal husbandry and agriculture, it is highly urgent to determine the quantification of antibiotics in biological systems by the simple, sensitive, and ...fast method. In this work, a novel nanoarchitecture of Co-based metal-organic frameworks (Co-MOF) and terephthalonitrile-based covalent organic framework (TPN-COF) was synthesized (represented by Co-MOF@TPN-COF), followed by the exploitation as the bioplatform of non-label aptasensor for detecting the most frequently used β-lactam antibiotics, ampicillin (AMP). The new porous hybrid material of Co-MOF@TPN-COF was synthesized by adding the as-prepared TPN-COF into the Co-MOF preparation system. The multilayered Co-MOF@TPN-COF nanosheets exhibit a high specific surface area (52.64 m2 g−1), nitrogen-rich groups and excellent electrochemical activity. As a result, large amounts of aptamer strands can be bound over the Co-MOF@TPN-COF nanosheets owning to the strong π–π stacking and hydrogen bonds. When detecting AMP by the electrochemical impedance spectroscopy, the fabricated Co-MOF@TPN-COF-based aptasensor exhibits an ultra-low detection limit of 0.217 fg mL−1 within the AMP concentration from 1.0 fg mL−1 to 2.0 ng mL−1, which was superior to those previously reported in literatures. In addition, this proposed aptasensor also shows high selectivity, good reproducibility and stability, acceptable regenerability, and favorable applicability in human serum, river water and milk. Therefore, the proposed Co-MOF@TPN-COF-based aptasensor has a great promise to be applied as a powerful tool in the fields of food safety.
•A novel 2D nanocomposite of Co-MOF and terephthalonitrile-based COF was synthesized.•Co-MOF@TPN-COF nanosheets with high specific surface area, nitrogen-rich groups and excellent electrochemical activity.•Co-MOF@TPN-COF-based aptasensor for ultra-sensitive detection of ampicillin.•Excellent selectivity, stability, reproducibility and applicability for detecting ampicillin.
A series of semiconductive CoNi bimetal–organic frameworks (CoxNi3-x(HAB)2 MOFs) were explored as the potential of the MOFs as efficient multifunctional electrocatalysts for the non-Pt methanol ...oxidation reaction (MOR) and overall water splitting in alkaline medium.
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As the efficient approaches for obtaining clean H2 energy, methanol oxidation (MOR) and water over slitting reactions have been increasingly essential. A series of novel semiconductive CoNi bimetal–organic framework (CoxNi3-x(HAB)2 MOF) have been prepared using hexaaminobenzene (HAB) as an organic linker. The obtained series of CoxNi3-x(HAB)2 MOFs were then explored as efficient multifunctional electrocatalysts for the non-Pt MOR and overall water splitting in alkaline medium. The basic characterizations of CoxNi3-x(HAB)2 MOFs revealed that they comprised multiple metal valence states (Co0/Co2+/Co3+ and Ni2+/Ni3+) and graphene-like nanostructures embedded with abundant CoNi alloy nanoparticles. Compared with the sole-metal MOFs (Co3(HAB)2 MOF and Ni3(HAB)2 MOF), the CoxNi3-x(HAB)2 MOF with a mass ratio of Co:Ni = 1:3 (CoxNi3-x(HAB)2 MOF-2) exhibited superior electrocatalytic performance for MOR. It gave a high current density of 92.8 mA cm−2 at 1.6 V vs. reversible hydrogen electrode (RHE) for MOR, along with the low overpotentials at the current density of 10 mV cm−2 (η10) and Tafel slopes toward hydrogen evolution reaction (η10 = 119 mV, Tafel slope = 46 mV dec-1) and oxygen evolution reaction (η10 = 1.35 V, Tafel slope = 26 mV dec−1). The analysis on the catalysis mechanism of MOR and water splitting in alkaline medium was also proposed. The voltages applied to the three- and two-electrode systems based on the bifunctional CoxNi3-x(HAB)2 MOF-2 catalyst for overall water splitting are 1.52 V vs. RHE and 1.45 V vs. silver/silver chloride (Ag/AgCl), respectively. This work provides a novel strategy for investigating the applications of promising two-dimensional semiconductive MOF as multifunctional electrocatalysts with boosted electrocatalytic activities in energy fields.
•COVID-19 infection can lead to the development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome MODS within a few days of disease onset.•A powerful cytokine ...storm accompanies COVID-19 pneumonia.•The capacity to accurately predict and intervene in the cytokine storm during COVID-19 pneumonia, as well as the ability to design effective specific strategies to block excessive inflammation, is critical for patient survival.
Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.
Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we ...developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8+ T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8+ T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.
Exopolysaccharide (EPS) was extracted and purified from Lactobacillus plantarum WLPL04, which has been confirmed previously as a potential probiotic for its antagonistic and immune-modulating ...activity. It has a molecular weight of 6.61 × 104 Da, consisting of xylose, glucose, and galactose in an approximate molar ratio of 3.4:1.8:1. Microstructural studies demonstrated that the EPS appeared as a smooth sheet structure with many homogeneous rod-shaped lumps. The preliminary in vitro assays indicated that the EPS could significantly inhibit the adhesion of Escherichia coli O157:H7 to HT-29 cells in competition, replacement, and inhibition assays at a dose of 1.0 mg/mL, with an inhibition rate of 20.24 ± 2.23, 29.71 ± 1.21, and 30.57 ± 1.73%, respectively. Additionally, the EPS exhibited strong inhibition against biofilm formation by pathogenic bacteria, including Pseudomonas aeruginosa CMCC10104, E. coli O157:H7, Salmonella Typhimurium ATCC13311, and Staphylococcus aureus CMCC26003. Furthermore, the EPS showed good inhibitory activity against the proliferation of HT-29 cells. The characteristics and bioactivities of this EPS may make it a promising candidate in developing functional food.
The unique physicochemical properties of two-dimensional (2D) graphene oxide (GO) could greatly benefit the biomedical field; however, recent research demonstrated that GO could induce in vitro and ...in vivo toxicity. We determined the mechanism of GO induced toxicity, and our in vitro experiments revealed that pristine GO could impair cell membrane integrity and functions including regulation of membrane- and cytoskeleton-associated genes, membrane permeability, fluidity and ion channels. Furthermore, GO induced platelet depletion, pro-inflammatory response and pathological changes of lung and liver in mice. To improve the biocompatibility of pristine GO, we prepared a series of GO derivatives including aminated GO (GO-NH2), poly(acrylamide)-functionalized GO (GO-PAM), poly(acrylic acid)-functionalized GO (GO-PAA) and poly(ethylene glycol)-functionalized GO (GO-PEG), and compared their toxicity with pristine GO in vitro and in vivo. Among these GO derivatives, GO-PEG and GO-PAA induced less toxicity than pristine GO, and GO-PAA was the most biocompatible one in vitro and in vivo. The differences in biocompatibility were due to the differential compositions of protein corona, especially immunoglobulin G (IgG), formed on their surfaces that determine their cell membrane interaction and cellular uptake, the extent of platelet depletion in blood, thrombus formation under short-term exposure and the pro-inflammatory effects under long-term exposure. Overall, our combined data delineated the key molecular mechanisms underlying the in vivo and in vitro biological behaviors and toxicity of pristine GO, and identified a safer GO derivative that could be used for future applications.
This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic ...control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.
Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of ...this technique is restricted by the paucity of suitable tumor-associated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (α-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, α-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8
T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by α-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, α-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine.
To predict the incidence of postoperative ileus in bladder cancer patients after radical cystectomy.
We retrospectively analyzed the perioperative data of 452 bladder cancer patients who underwent ...radical cystectomy with urinary diversion at the Second Hospital of Tianjin Medical University between 2016 and 2021. Univariate and multivariate logistic regression were used to identify the risk factors for postoperative ileus. Finally, a nomogram model was established and verified based on the independent risk factors.
Our study revealed that 96 patients (21.2%) developed postoperative ileus. Using multivariate logistic regression analysis, we found that the independent risk factors for postoperative ileus after radical cystectomy included age > 65.0 years, high or low body mass index, constipation, hypoalbuminemia, and operative time. We established a nomogram prediction model based on these independent risk factors. Validation by calibration curves, concordance index, and decision curve analysis showed a strong correlation between predicted and actual probabilities of occurrence.
Our nomogram prediction model provides surgeons with a simple tool to predict the incidence of postoperative ileus in bladder cancer patients undergoing radical cystectomy.
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