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Metal–organic framework (UiO-66) derived nanoporous carbon/electrochemically reduced graphene oxide nanocomposite (UiO-66/NPC/ERGO) was developed to fabricate an electrochemical sensor for achieving efficient detection of methyl parathion (MP) residues in food. The carbonization derivative UiO-66/NPC was synthesized by one-step pyrolysis with only UiO-66 precursor. Based on the synergistic effect of enough active absorption sites and specific absorption of UiO-66/NPC for MP as well as the high conductivity of ERGO, the UiO-66/NPC/ERGO sensor exhibited excellent sensing performance. Under the optimal conditions, a linear determination range of 20–4000 ng/mL and low limit of detection (LOD) of 0.395 ng/mL for MP was obtained by direct electrochemical oxidation using SWV. Additionally, the sensor provided excellent stability and selectivity, as well as effective determination of real samples with satisfactory recoveries (98.5–104.0%), manifesting that the UiO-66/NPC/ERGO has great potential for organophosphorus pesticide detection. Graphical Abstract

Amino functionalized zirconium-based metal–organic framework (NH 2 -UiO-66) and zinc-based zeolitic imidazolate framework (ZIF-8) were integrated to develop a core–shell architectured hybrid material (NH 2 -UiO-66@ZIF-8, NU66@Z8). The morphology and structure evolutions of core–shell NU6@Z8 were investigated by FE-SEM, XRD, FTIR, and XPS. The NU66@Z8 combined with carboxylated multi-walled carbon nanotubes (CMWCNT) was deposited on a glassy carbon electrode (GCE) for fabricating an electrochemical platform towards detecting Pb 2+ and Cu 2+ . The NU66@Z8/CMWCNT/GCE revealed significantly improved electrochemical performance for determination of Pb 2+ and Cu 2+ compared with the individual components, which can be attributed to the strong adsorption capacity, unique core–shell structure, and large electrochemical active surface area of NU66@Z8/CMWCNT. Under the optimal conditions, the developed sensor exhibited excellent sensing capability with a low limit of detection (Pb 2+ ,1 nM; Cu 2+ , 10 nM) and a wide determination range (Pb 2+ ,0.003–70 μM; Cu 2+ , 0.03–50 μM). The sensor showed high selectivity towards common interfering ions and good repeatability. The real sample recoveries of proposed sensor were in the range 95.0–103% for Pb 2+ (RSD ≤ 5.3%) and 94.2–106% for Cu 2+ (RSD ≤ 5.9%), suggesting that the NU66@Z8/CMWCNT is suitable for examining trace heavy metals in natural environment. Graphical Abstract

Amino functionalized zirconium-based metal-organic framework (NH.sub.2-UiO-66) and zinc-based zeolitic imidazolate framework (ZIF-8) were integrated to develop a core-shell architectured hybrid material (NH.sub.2-UiO-66@ZIF-8, NU66@Z8). The morphology and structure evolutions of core-shell NU6@Z8 were investigated by FE-SEM, XRD, FTIR, and XPS. The NU66@Z8 combined with carboxylated multi-walled carbon nanotubes (CMWCNT) was deposited on a glassy carbon electrode (GCE) for fabricating an electrochemical platform towards detecting Pb.sup.2+ and Cu.sup.2+. The NU66@Z8/CMWCNT/GCE revealed significantly improved electrochemical performance for determination of Pb.sup.2+ and Cu.sup.2+ compared with the individual components, which can be attributed to the strong adsorption capacity, unique core-shell structure, and large electrochemical active surface area of NU66@Z8/CMWCNT. Under the optimal conditions, the developed sensor exhibited excellent sensing capability with a low limit of detection (Pb.sup.2+,1 nM; Cu.sup.2+, 10 nM) and a wide determination range (Pb.sup.2+,0.003-70 [mu]M; Cu.sup.2+, 0.03-50 [mu]M). The sensor showed high selectivity towards common interfering ions and good repeatability. The real sample recoveries of proposed sensor were in the range 95.0-103% for Pb.sup.2+ (RSD [less than or equal to] 5.3%) and 94.2-106% for Cu.sup.2+ (RSD [less than or equal to] 5.9%), suggesting that the NU66@Z8/CMWCNT is suitable for examining trace heavy metals in natural environment. Graphical

Amino functionalized zirconium-based metal-organic framework (NH -UiO-66) and zinc-based zeolitic imidazolate framework (ZIF-8) were integrated to develop a core-shell architectured hybrid material (NH -UiO-66@ZIF-8, NU66@Z8). The morphology and structure evolutions of core-shell NU6@Z8 were investigated by FE-SEM, XRD, FTIR, and XPS. The NU66@Z8 combined with carboxylated multi-walled carbon nanotubes (CMWCNT) was deposited on a glassy carbon electrode (GCE) for fabricating an electrochemical platform towards detecting Pb and Cu . The NU66@Z8/CMWCNT/GCE revealed significantly improved electrochemical performance for determination of Pb and Cu compared with the individual components, which can be attributed to the strong adsorption capacity, unique core-shell structure, and large electrochemical active surface area of NU66@Z8/CMWCNT. Under the optimal conditions, the developed sensor exhibited excellent sensing capability with a low limit of detection (Pb ,1 nM; Cu , 10 nM) and a wide determination range (Pb ,0.003-70 μM; Cu , 0.03-50 μM). The sensor showed high selectivity towards common interfering ions and good repeatability. The real sample recoveries of proposed sensor were in the range 95.0-103% for Pb (RSD ≤ 5.3%) and 94.2-106% for Cu (RSD ≤ 5.9%), suggesting that the NU66@Z8/CMWCNT is suitable for examining trace heavy metals in natural environment.

Aflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

Diabetes Mellitus can cause dental pulp cells apoptosis by oxidative stress, and affect the integrity and function of dental pulp tissue. Mitochondria are the main attack targets of oxidative stress and have a critical role in apoptosis. However, whether mitochondria are involved in dental pulp damage caused by diabetes mellitus remains unclear. This study aimed to investigate the role of mitochondria in the apoptosis of odontoblast-like cell line (mDPC6T) induced by glucose oxidative stress, and to explore its possible mechanism. We established an oxidative stress model in vitro using glucose oxidase/glucose to simulate the pathological state under diabetic conditions. We found that the opening of mitochondrial permeability transition pore (mPTP) contributed to the apoptosis of mDPC6T treated with glucose oxidase, as evidenced by enhanced mitochondrial reactive oxygen species (mtROS) and intracellular Ca 2+ disorder, significantly reduced mitochondrial membrane potential (MMP) and ATP production. Antioxidant N-acetylcysteine (NAC) or Cyclosporine A (mPTP inhibitor) blocked the mPTP opening, which significantly attenuated mitochondrial dysfunction and apoptosis induced by glucose oxidative stress. In addition, we found that glucose oxidative stress stimulated mPTP opening may through inhibition of Akt-GSK3β pathway. This study provides a new insight into the mitochondrial mechanism underlying diabetes-associated odontoblast-like cell apoptosis, laying a foundation for the prevention and treatment of diabetes-associated pulp injury.

Currently, immunotherapy has been a backbone in the treatment of advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, only a small proportion of NSCLC patients respond to immune checkpoint inhibitors, and majority of patients with initial response will develop acquired resistance at 5 years, which usually manifests as oligo-progression or oligo-metastases. Evidence from multiple clinical trials indicates that local consolidative therapies could improve the prognosis of oligometastatic NSCLC patients. Herein, we reported a case of advanced squamous lung cancer which showed a durable abscopal effect from microwave ablation after acquired resistance of immunotherapy.

Inflammation drives the development of multiple inflammatory enterohepatic diseases. The recruitment of immune cells to inflammatory tissues is essential for maintaining immune homeostasis, mediating immune responses and regulating inflammation. MAdCAM-1/α4β7 is a pair of homing ligand and receptor that plays important roles in lymphocyte migration. Their binding induces lymphocytes to cross endothelial structures into corresponding lymphoid tissues, contributing to the inflammatory response. Aberrant lymphocyte migration due to excessive binding is closely related to the occurrence and development of inflammatory bowel disease and liver inflammation. In this review, we focus on the activation of α4β7 and binding to MAdCAM-1 how to induce the migration of multiple kinds of lymphocytes. Additionally, we describe the intestinal microbiota and its metabolites associated with MAdCAM-1/α4β7 in inflammatory enterohepatic diseases. We also discuss the current status of the development of monoclonal antibodies and small molecule drugs targeting MAdCAM-1/α4β7 for the remission and treatment of inflammatory enterohepatic disease. Future research should focus on enhancing hepatic specificity and conducting well-designed clinical trials for inflammatory liver diseases to confirm therapeutic efficacy.

Vibrio parahaemolyticus is an important halophilous pathogen that can cause not only a broad range of disease in aquatic animals but also serious seafood-borne illness in humans as a result of the consumption of seafood. To avoid the use of antibiotics, it is critical to identify protective antigens for developing highly effective vaccines against this pathogen. Outer membrane proteins (OMPs) have been suggested as potential vaccine candidates for conferring protection against infection. In this study, we identified novel immunogenic OMPs using an immune assay with serum antibodies from mice infected by V. parahaemolyticus combined with mass spectrometry analysis. Nine OMPs were identified to be immunogenic proteins, and four of these identified proteins with relatively low abundance in OMP profiles, LptD, VP0802, VP1243 and VP0966, were determined to have immunogenicity for the first time. One OMP of interest, VP0802, is highly conserved among major Vibrio species and was proposed to adopt a β-barrel conformation and to be a member of the OprD protein family by bioinformatic analysis. The immunogenicity and protective efficacy of VP0802 were further evaluated by bacterial challenge postimmunization in a mouse model. VP0802 was confirmed to be highly immunogenic and to offer strong protection against V. parahaemolyticus infection, with an RPS of at least 66.7. Efficient clearance of bacteria from the blood of vaccinated mice was also observed. Moreover, upregulation of VP0802 expression was found after bacteria were exposed to fresh sera. These data, taken together, suggest that VP0802 is a promising candidate for the development of a subunit vaccine to prevent V. parahaemolyticus infection.

Outer membrane proteins (OMPs) are unique to Gram-negative bacteria. Several features, including surface exposure, conservation among strains and ability to induce immune responses, make OMPs attractive targets for using as vaccine antigens and immunotherapeutics. LptD is an essential OMP that mediates the final transport of lipopolysaccharide (LPS) to outer leaflet. The protein in Vibrio parahaemolyticus was identified to have immunogenicity in our previous report. In this study, broad distribution, high conservation and similar surface-epitopes of LptD were found among the major Vibrio species. LptD was further revealed to be associated with immune responses, and it has a strong ability to stimulate antibody response. More importantly, it conferred 100% immune protection against lethal challenge by V. parahaemolyticus in mice when the mice were vaccinated with LptD, and this finding was consistent with the observation of efficient clearance of bacteria in vaccination mice. Strikingly, targeting of bacteria by the LptD antibody caused significant decreases in both the growth and LPS level and an increase in susceptibility to hydrophobic antibiotics. These findings were consistent with those previously obtained in lptD -deletion bacteria. These data demonstrated LptD is a promising vaccine antigens and a potential target for antibody-based therapy to protect against Vibrio infections.