Precise Control of Metal Active Sites of Metal-Organic Framework Nanozymes for Achieving Excellent Enzyme-Like Activity and Efficient Pancreatitis Therapy.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease that can lead to the development of systemic inflammatory response syndrome and its progression to severe acute pancreatitis. Hence, there is an urgent need for the rational design of highly efficient antioxidants to treat AP. Herein, an optimized Cu-based metal-organic framework (MOF) nanozyme with exceptional antioxidant activity is introduced, designed to effectively alleviate AP, by engineering the metal coordination centers in MN2Cl2 (M = Co, Ni, Cu). Specifically, the Cu MOF, which benefits from a Cu active center similar to that of natural superoxide dismutase (SOD), exhibited at least four times higher SOD-like activity than the Ni/Co MOF. Theoretical analyses further demonstrate that the CuN2Cl2 site not only has a moderate adsorption effect on the substrate molecule •OOH but also reduces the dissociation energy of the product H2 O2 . Additionally, the Cu MOF nanozyme possesses the excellent catalase-like activity and •OH removal ability. Consequently, the Cu MOF with broad-spectrum antioxidant activity can efficiently scavenge reactive oxygen species to alleviate arginine-induced AP. More importantly, it can also mitigate apoptosis and necrosis of acinar cells by activating the PINK1/PARK2-mediated mitophagy pathway. This study highlights the distinctive functions of tunable MOF nanozymes and their potential bio-applications.

Using Wool Keratin Derived Metallo-Nanozymes as a Robust Antioxidant Catalyst to Scavenge Reactive Oxygen Species Generated by Smoking.

Self-assembled nanostructures based on biomolecules (e.g., proteins and amino acids) and metal ions have promising applications in mimicking the nanostructure, properties, and functions of natural enzymes. Herein, a metal ion-mediated self-assembly method for constructing catalytically active Cu-wool-keratin (CuWK) two-dimensional nanozymes is presented. Specifically, by introducing copper ions as abiological cofactors, WK can serve as a protein scaffold to design and create Cu catalytic sites. The optimized hybrids with Cu-WK coordination framework exhibit significant superoxide dismutases-like activity, catalase-like activity, and hydroxyl radical scavenging ability. These combined antioxidant activities make CuWK a robust nanozyme to effectively remove various reactive oxygen species (ROS). In this work, the as-prepared CuWK as a new additive can be integrated into a cigarette filter system to effectively remove the produced ROS from the burning of tobacco. More importantly, the CuWK nanozymes as a critical element can be further utilized to construct a recycling cigarette holder. Therefore, the present work shows that nanozymes with advanced catalytic capabilities can be constructed by self-assembly of metal ions and proteins, thus facilitating the rational design and discovery of this kind of artificial metalloenzymes.

A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.

High Carbonization Temperature to Trigger Enzyme Mimicking Activities of Silk-Derived Nanosheets.

Herein, it is demonstrated that N-rich carbonized silk fibroin materials (CSFs) can serve as efficient peroxidase, and oxidase mimics. Their enzyme-like activities are highly dependent on carbonization conditions. CSFs obtained at low temperatures do not exhibit significant catalytic reactivity, while their enzyme-like catalysis performance is greatly activated after high-temperature treatment. Such a phenomenon is mainly ascribed to the increase of graphitization degree and graphitic nitrogen and the emergence of disordered graphitic structures during the formation of turbostratic carbon. In addition, inspired by the excellent photothermal conversion efficiency, and temperature-dependent catalytic behavior of CSFs, near-infrared light can be used to remotely control their enzyme-like activities. More importantly, as-prepared robust silk-derived nanosheets can be applied to photothermal-catalytic cancer therapy and sensing. It is believed that such a smart artificial enzyme system will throw up exciting new opportunities for the chemical industry and biotechnology.

Bleeding Meckel Diverticulum: A Retrospective Analysis of Computed Tomography Enterography Findings.

OBJECTIVE: The aim of this study was to evaluate the computed tomography enterography (CTE) characteristics of bleeding Meckel diverticulum. METHODS: The CTE images of 35 patients with Meckel diverticulum and gastrointestinal bleeding were retrospectively evaluated. RESULTS: Meckel diverticulum was visualized in 33 of 35 patients and located in the right lower abdomen (20/33), midline lower abdomen (8/33), left lower abdomen (3/33), or paramedially near the umbilicus (2/33). The Meckel diverticulum was visualized on the antimesenteric side of the ileum in 16 patients (48.5%) and pointed toward the umbilicus in 10 (30.3%). The diverticulum appeared as a blind-ended tubular (22/33 [66.7%]) or saccular (11/33 [33.3%]) bowel segment. Separated supplying vessel was identified in 15 patients (45.5%) and associated with diverticulum (P = 0.037). The ectopic tissue was pathologically confirmed in 11 (33.3%) of 33 patients and was associated with diverticular nodules (P = 0.002). CONCLUSIONS: Awareness of CTE features could aid in the preoperative assessment of bleeding Meckel diverticulum.

The clinical characteristics of Chinese patients with unilateral renal agenesis.

BACKGROUND: We aimed to investigate the clinical characteristics of Chinese patients with unilateral renal agenesis. METHODS: We enrolled patients with unilateral renal agenesis diagnosed radiologically at the Department of Nephrology from January 2008 to January 2016. Patients with a solitary kidney due to nephrectomy or renal atrophy due to secondary factors were excluded. Clinical data were recorded and analyzed. RESULTS: In this study, 118 Chinese patients with unilateral renal agenesis were recruited, and the gender ratio (male/female) was 1.11:1. A total of 14 (11.9%) patients had additional abnormalities, 15 (12.7%) had a family history, and 30 (25.4%) presented with renal insufficiency. Kidney length, serum creatinine level and estimated glomerular filtration rate were significantly different between patients with and without family history (P < 0.05, respectively). Gender showed a significant difference between patients with and without other abnormalities. Kidney length and the incidence of proteinuria, hematuria, hypertension, and hyperuricemia were significantly different between patients with and without renal insufficiency. Logistic regression analysis revealed that family history was associated with severe renal failure (OR = 7.11, 95% CI 1.52-33.25). CONCLUSION: Renal insufficiency is common in patients with unilateral renal agenesis. Patients with renal insufficiency have shorter kidney lengths and a higher incidence of proteinuria, hypertension, hematuria, and hyperuricemia. Family history is considered a risk factor for severe renal failure.

LncRNA, CRNDE promotes osteosarcoma cell proliferation, invasion and migration by regulating Notch1 signaling and epithelial-mesenchymal transition.

Osteosarcoma is the most common bone malignancy in adolescence. Recently, the long non-coding RNAs (lncRNAs) were reported to play important roles in osteosarcoma progression. The present study examined the potential role of the lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE) and molecular mechanisms underlying osteosarcoma progression. In the present study, we identified that CRNDE was up-regulated in osteosarcoma tissues and cell lines, and CRNDE expression level was significantly higher in osteosarcoma tissues from patients with advanced stage and metastasis. Overexpression of CRNDE promoted cell growth, cell proliferation, cell invasion and migration, and increased cell population at S phase with a decreased cell population at G0/G1 phase in MG-63 cells. Knock-down of CRNDE suppressed cell growth, cell proliferation, cell invasion and migration, and decreased cell population at S phase with an increased cell population at G0/G1 phase in U2OS cells. Overexpression of CRNDE was found to enhance the activity of Notch1 signaling and promote epithelial-mesenchymal transition (EMT) in MG-63 cells, while knock-down of CRNDE exerted the opposite effects in U2OS cells. The in vivo results showed that knock-down of CRNDE suppressed the tumor growth in the nude mice inoculated with osteosarcoma cells, and knock-down of CRNDE also suppressed the mRNA expression of Notch1, JAG1, N-cadherin, vimentin, and increased the mRNA expression of E-cadherin in the tumor tissues. Collectively, our results indicated that CRNDE functioned as an oncogene in osteosarcoma cell lines, and CRNDE may exert its oncogenic role via regulating Notch1 signaling and EMT in osteosarcoma.

Identification of 8 Novel Mutations in Nephrogenesis-Related Genes in Chinese Han Patients with Unilateral Renal Agenesis.

BACKGROUND: Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA. METHODS: Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods. Patients with a solitary kidney owing to nephrectomy or renal atrophy due to secondary factors were excluded. Nine (10.5%) patients had a family history of abnormal nephrogenesis. Fifteen (17.4%) had other malformations in the urogenital system. All coding exons and adjacent intron regions of 25 genes were analyzed using next-generation sequencing and validated by Sanger sequencing and 100 ethnically matched healthy controls. RESULTS: Ten conserved mutations (9 missense mutations and 1 deletion mutation) were identified in SALL1, EYA1, RET, HNF1B, DSTYK, WNT4, and SIX5. All mutations were novel or rare (frequency <0.1%) in the public databases and absent from the 100 healthy controls. Nine patients carried mutations in candidate genes. Most of the patients carried one single heterozygous mutation, except for 2, who respectively carried compound heterozygous mutations and 2 single heterozygous mutations. In addition, 2 patients shared the same mutation in DSTYK. CONCLUSION: A total of 10.5% of our URA cases could be explained by mutations in our candidate genes. The mutations in nephrogenesis-related genes in the Chinese Han patients with URA had a decentralized distribution without any hotspot mutations.

Using Cu-Based Metal-Organic Framework as a Comprehensive and Powerful Antioxidant Nanozyme for Efficient Osteoarthritis Treatment.

Developing nanozymes with effective reactive oxygen species (ROS) scavenging ability is a promising approach for osteoarthritis (OA) treatment. Nonetheless, numerous nanozymes lie in their relatively low antioxidant activity. In certain circumstances, some of these nanozymes may even instigate ROS production to cause side effects. To address these challenges, a copper-based metal-organic framework (Cu MOF) nanozyme is designed and applied for OA treatment. Cu MOF exhibits comprehensive and powerful activities (i.e., SOD-like, CAT-like, and •OH scavenging activities) while negligible pro-oxidant activities (POD- and OXD-like activities). Collectively, Cu MOF nanozyme is more effective at scavenging various types of ROS than other Cu-based antioxidants, such as commercial CuO and Cu single-atom nanozyme. Density functional theory calculations also confirm the origin of its outstanding enzyme-like activities. In vitro and in vivo results demonstrate that Cu MOF nanozyme exhibits an excellent ability to decrease intracellular ROS levels and relieve hypoxic microenvironment of synovial macrophages. As a result, Cu MOF nanozyme can modulate the polarization of macrophages from pro-inflammatory M1 to anti-inflammatory M2 subtype, and inhibit the degradation of cartilage matrix for efficient OA treatment. The excellent biocompatibility and protective properties of Cu MOF nanozyme make it a valuable asset in treating ROS-related ailments beyond OA.

Adenosquamous carcinoma of the pancreas: multidetector-row computed tomographic manifestations and tumor characteristics.

OBJECTIVE: The purpose of this article was to present the adenosquamous carcinoma (ASqC) of the pancreas: multidetector-row computed tomographic (CT) features and tumor characteristics. MATERIALS AND METHODS: The clinical data and CT studies of 12 patients with pathologically proven ASqC of the pancreas between the dates February 2001 and February 2010 were retrospectively analyzed. RESULTS: The presenting symptoms of ASqC of the pancreas were nonspecific. Elevated serum levels of carbohydrate antigen 19-9, carbohydrate antigen 12-5, and carcinoembryonic antigen were noted. The tumor was most commonly involved in the pancreatic head in 6 patients, with the dilation of the common bile duct and the upstream main pancreatic duct. All ASqCs exhibited invasive growth. No calcification and intratumoral hemorrhage were noted in ASqCs. Ten tumors showed enhancement in the early arterial phase and persistent enhancement in the portal vein phase. CONCLUSION: The typical CT appearance of ASqC was solitary oval or round without any capsule and a defined margin. The dilation of the main pancreatic duct and/or the common bile duct was always discovered. The huge infiltrative lesion outside the pancreas was detected in the tail and/or the body of the pancreas. Not only the elevation of carbohydrate antigen 19-9 is common, but also Ca12-5 and CEA, whereas human alpha fetoprotein elevation is not observed. The enhancement pattern of tumor showed persistence in the portal vein phase.

A Rational Design of Metal-Organic Framework Nanozyme with High-Performance Copper Active Centers for Alleviating Chemical Corneal Burns.

Metal-organic frameworks (MOFs) have attracted significant research interest in biomimetic catalysis. However, the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge. Inspired by metalloenzymes with well-defined coordination structures, a series of MOFs containing halogen-coordinated copper nodes (Cu-X MOFs, X = Cl, Br, I) are employed to elucidate their structure-activity relationship. Intriguingly, experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center. The optimal Cu-Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes. More importantly, by performing enzyme-mimicking catalysis, the Cu-Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress, thus effectively relieving ocular chemical burns. Mechanistically, the antioxidant and antiapoptotic properties of Cu-Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways. Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and, more significantly, demonstrating their potential therapeutic effect in ophthalmic disease.

Quantitative measures of comb sign in Crohn's disease: correlation with disease activity and laboratory indications.

To determine retrospectively if quantitative measures of the comb sign at CT enterography correlated with laboratory indications in Crohn's disease. We retrospectively included 72 known CD patients (47 male and 25 female patients) and 41 normal controls who had undergone CT enterography (CTE) from 2008 to 2010 and had high-sensitive C reaction protein (Hs-CRP) and erythrocyte sedimentation rate (ESR) results. We divided the 72 CD patients into two groups based on disease activity which was determined by Rutgeerts' score. 41 patients were characterized as active disease while 31 patients were as inactive disease. For each individual, one reformatted coronal CTE image in which the comb sign (vasa recta) was most obviously displayed was selected by two experienced radiologists in a double blind manner. For each image, 20 regions of interest (ROI) with area of 1 cm(2) were drawn and placed over the site where the comb sign exists; the comb sign amount was counted in each ROI and recorded. Total amount of the comb sign were assessed from 20 ROI data. Quantitative comb sign results were compared with Hs-CRP and ESR level. Quantitative comb sign score is significantly higher in the CD group than in the control group at both the arterial stage and venous stage (P < 0.001). Quantitative comb sign score is obviously higher in active CD patients than in inactive CD patients both at arterial stage and venous stage (3.63 vs. 2.86 at arterial stage; 3.53 vs. 2.90 at venous stage). ESR level was well correlated with quantitative comb sign score both at arterial and venous stage whereas Hs-CRP has no significant correlation at either stage. Quantitative comb sign results did well in predicting CD activity with the accuracy rate of 78.4% at arterial stage and 80% at venous stage when using 3.33 as the cutoff of quantitative comb sign score. Quantitative comb sign score is a promising CTE parameter in predicting CD activity and be well correlates with the ESR level.

ZIF-90 with biomimetic Zn-N coordination structures as an effective nanozyme to mimic natural hydrolase.

Inspired by the structures of enzymes, a fast and robust strategy for generating ZIF-90 metallo-nanozymes is presented. The Zn-N coordination structure in ZIF-90 can closely imitate the catalytic center of a natural zinc-based hydrolase. As expected, ZIF-90 possesses potent hydrolase-mimicking activity, high stability and excellent recyclability.

Imaging features of small intestinal amyloidosis: a case report.

Amyloidosis is a rare disease characterized by forming pathological protein deposits in organs or tissues. The localized form of amyloidosis affecting small intestine is rare. We report a case of small intestine amyloidosis which presented gastrointestinal bleeding and abdominal pain. We also display radiologic features of amyloidosis of the small bowel which will add evidence to accurate diagnosis and management.

Recent Advances in Patterning Natural Polymers: From Nanofabrication Techniques to Applications.

The development of a flexible and efficient strategy to precisely fabricate polymer patterns is increasingly significant for many research areas, especially for cell biology, pharmaceutical science, tissue engineering, soft photonics, and bioelectronics. Recent advances of patterning natural polymers using various nanofabrication techniques, including photolithography, electron-beam lithography, dip-pen nanolithography, inkjet printing, soft lithography, and nanoimprint lithography are discussed here. Integrating nanofabrication techniques with naturally derived macromolecules provides a feasible route for transforming these polymer materials into versatile and sophisticated devices while maintaining their intrinsic and excellent properties. Furthermore, the corresponding applications of these natural polymer patterns generated by the above techniques are elaborated. In the end, a summary of this promising research field is offered and an outlook for the future is given. It is expected that advances in precise spatial patterns of natural polymers would provide new avenues for various applications, such as tissue engineering, flexible electronics, biomedical diagnosis, and soft photonics.

Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai.

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited. Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia. Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected. Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09-52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80-9.38). Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.

Advances in Synchrotron Radiation-based X-ray Absorption Spectroscopy to Characterize the Fine Atomic Structure of Single-atom Nanozymes.

Single-atom nanozymes (SAzymes) with high atomic utilization, excellent catalytic activities, and selectivity have recently attracted significant interest. Usually, they contain only isolated metal atoms embedded in host matrices. However, traditional measuring instruments are extremely difficult to obtain their useful structural information due to ultra-low metal loading, amorphous structure, coordination with light-weight surface atoms and/or co-existing of other metal elements. Synchrotron radiation-based X-ray absorption fine structure spectroscopy (XAFS) has demonstrated its usefulness for this type of catalyst. In this mini-review, we have summarized the recent progress using XAFS to characterize the fine atomic structure of these nanozymes. The synthetic strategies of SAzymes, the principle of XAFS, delicate structural information by XAFS, and the applications of SAzymes have been presented. Furthermore, the outlook and challenges in this active research field have also been discussed. We expect that the help of XAFS can offer a wealth of opportunities to design and develop more efficient SAzymes and apply them to various fields.

Wool Keratin Photolithography as an Eco-Friendly Route to Fabricate Protein Microarchitectures.

Herein, we present an eco-friendly route to construct protein microarchitectures by using wool keratin (WK) as a green biophotoresist. The photoactive WK was extracted from wool with a method of alkaline hydrolysis and reacted with 2-isocyanatoethyl methacrylate (IEM). The whole process can avoid the use of surfactant and does not cause apparent changes in the structure and function of WK. With the aid of direct-write photolithography, "photoresist-like" WK can be further used for fabricating well-defined and high-performance patterns at a low micron-scale (µm) without high temperature, complicated process, long time, and high production cost.

Hot-Electron-Activated Peroxidase-Mimicking Activity of Ultrathin Pd Nanozymes.

Light-activated nanozymes can provide a wealth of new opportunities for the chemical industry and biotechnology. However, present remote-controlled catalytic systems are still far from satisfactory. Herein, we present an interesting example of applying ultrathin Pd nanosheets (Pd NSs) as a light-controllable peroxidase mimic. Since most of Pd atoms are exposed on their surface, Pd NSs with a thickness of 1.1 nm possess high peroxidase-like activity. More importantly, under light excitation, such intrinsic activity can be further activated by a nearly 2.4- to 3.2-fold. Such a phenomenon can be ascribed to the unique optical property of ultrathin Pd NSs, which can efficiently capture photons to generate hot electrons via surface plasmon resonance effect and thus promote the in situ decomposition of H2O2 into reactive oxygen species radicals (O*). This enhanced catalysis can also be used for real-time and highly sensitive colorimetric detection of H2O2. We expect our work can provide valuable insights into the rational design of artificial nanozymes with controllable and efficient activity in biomedical diagnostics, drug delivery, and environmental chemistry.

Constructing dual-readout logic operations based on the silk fibroin sol-gel transition.

Inspired by an H2O2-induced chemical gelation of silk fibroin (SF) and biochemical computing, we demonstrated for the first time that the phase transformation of SF can serve as a visual output signal for constructing multiple Boolean logic operations. In our biological logic gates, three common enzymes, ß-galactosidase (ß-Gal), glucose oxidase (GOx) and catalase (CAT), were used as inputs and the SF state (sol or gel) was defined as an output. The designed logic gates could be observed by the naked eye and UV-Vis absorption change. Since a distinctive advantage of biocomputing is that different enzymatic reactions can take place smoothly when they work together, our logic system could be further scaled up to generate a multi-input logic network without any "crosstalk" and interference between them. We hope that such a constructed system might help us understand complex physiological processes in living systems, and have potential applications in digital bio-diagnosis.