Poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) and its copolymer hydrogels are typical polyelectrolyte gels with extremely high swelling capacity that are widely used in industry. It's common to ...consider these hydrogels as weak materials that are difficult to toughen. Reported here is a facile strategy to transform swollen and weak poly(acrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) P(AAm‐co‐AMPS) hydrogels to tough ones by forming strong sulfonate–Zr4+ metal‐coordination complexes. The resultant hydrogels with moderate water content possess high stiffness, strength, and fracture energy, which can be tuned over 3–4 orders of magnitude by controlling the composition and metal‐to‐ligand ratio. Owing to the dynamic nature of the coordination bonds, these hydrogels show rate‐ and temperature‐dependent mechanical performances, as well as good self‐recovery properties. This strategy is universal, as manifested by the drastically improved mechanical properties of hydrogels of various natural and synthetic sulfonate‐containing polymers. The toughened hydrogels can be converted to the original swollen ones by breaking up the metal‐coordination complexes in alkaline solutions. The reversible brittle–tough transition and concomitant dramatic volume change of polyelectrolyte hydrogels afford diverse applications, as demonstrated by the design of a tubular grasper with holding force a thousand times its own weight for objects with different geometries. It is envisioned that these hydrogels enable versatile applications in the biomedical and engineering fields.
Reversible transformation of polyelectrolyte hydrogels between swollen, weak states and collapsed, tough states is realized by formation and breaking up of robust metal‐coordination complexes. The dramatic variations of the gels’ volume and mechanical properties over 3–4 orders of magnitude enable the design of a hydrogel‐based tubular grasper with high holding force, i.e., thousand times its own weight, to grip objects with different geometries.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We report a 2-family cluster of persons infected with severe acute respiratory syndrome coronavirus 2 in the city of Zhoushan, Zhejiang Province, China, during January 2020. The infections resulted ...from contact with an infected but potentially presymptomatic traveler from the city of Wuhan in Hubei Province.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small ...molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.
Hydrocarbons are still the most important precursors of functionalized organic molecules, which has stirred interest in the discovery of new C−H bond functionalization methods. We describe herein a ...new step‐economical approach that enables C−C bonds to be constructed at the terminal position of linear alkanes. First, we show that secondary alkyl bromides can undergo in situ conversion into alkyl zinc bromides and regioconvergent Negishi coupling with aryl or alkenyl triflates. The use of a suitable phosphine ligand favoring Pd migration enabled the selective formation of the linear cross‐coupling product. Subsequently, mixtures of secondary alkyl bromides were prepared from linear alkanes by standard bromination, and regioconvergent cross‐coupling then provided access to the corresponding linear arylation product in only two steps.
Remote control: Secondary alkyl bromides underwent regioconvergent Barbier–Negishi coupling with aryl triflates in the presence of a phosphine ligand favoring Pd migration to give linear products with good to high linear/branched selectivity (see scheme). This procedure was also applied to mixtures of secondary alkyl bromides, prepared from linear alkanes by standard bromination.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Vascular restenosis after balloon dilation is largely caused by the over‐proliferation of smooth muscle cells, which is triggered and exacerbated by local excessive inflammation and oxidative stress. ...The excessive inflammatory and oxidative stress cause tissue/cell damage, hamper endothelial functions, and worsen intimal hyperplasia and restenosis. A high level of reactive oxygen species (ROS) overproduction is regarded as the main culprit. Therefore, efficiently inhibiting ROS over‐production or weightily depleting them is of great significance. Herein, a “ROS‐responsive/scavenging prodrug” is introduced into balloon coating for the treatment of vascular restenosis. A reversible phenylboronic ester‐bearing caffeic acid (CA) macromolecular prodrug (PBC) is designed for the controlled and on‐demand dual‐drug release triggered by the local high ROS level; the released CA and 4‐hydroxybenzyl alcohol exhibit efficient antioxidant and anti‐inflammatory effects by scavenging ROS, thereby regulating vascular microenvironment and protecting endothelium functions. To accelerate endothelium regeneration, pro‐endothelial microRNA‐126 is further introduced. The ROS‐responsive/scavenging prodrug/miRNA balloon coating efficiently prevents intimal hyperplasia, alleviates local inflammation, and improves endothelium healing in a rat abdominal aorta restenosis model, which may provide applicative perspectives for next‐generation drug‐coated balloons and other cardiovascular diseases treatment.
A reversible phenylboronic ester‐bearing caffeic acid (CA) macromolecular prodrug (PBC) is designed for the controlled and on‐demand dual‐antioxidant release (CA and 4‐hydroxybenzyl alcohol (HBA)) triggered by the local high reactive oxygen species (ROS) level, thereby exhibiting antioxidant and anti‐inflammatory effects; the pro‐endothelial microRNA‐126 is introduced to further accelerate endothelialization. This ROS‐responsive/scavenging prodrug/miRNA balloon coating efficiently inhibits long‐term vascular restenosis.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch ...signaling was activated by inducible EC‐specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC‐associated genes and increased continuous EC‐associated genes, suggesting LSEC dedifferentiation. Consistently, endothelial Notch activation enhanced hepatic fibrosis (HF) induced by CCl4. Notch activation attenuated endothelial nitric oxide synthase (eNOS)/soluble guanylate cyclase (sGC) signaling, and activation of sGC by 3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzylindazole (YC‐1) reversed the dedifferentiation phenotype. In addition, Notch activation subverted the hepatocyte‐supporting angiocrine profile of LSECs by down‐regulating critical hepatocyte mitogens, including Wnt2a, Wnt9b, and hepatocyte growth factor (HGF). This led to compromised hepatocyte proliferation under both quiescent and regenerating conditions. Whereas expression of Wnt2a and Wnt9b was dependent on eNOS‐sGC signaling, HGF expression was not rescued by the sGC activator, suggesting heterogeneous mechanisms of LSECs to maintain hepatocyte homeostasis. Conclusion: Endothelial Notch activation results in LSEC dedifferentiation and accelerated liver fibrogenesis through eNOS‐sGC signaling, and alters the angiocrine profile of LSECs to compromise hepatocyte proliferation and liver regeneration (LR). (Hepatology 2018).
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Two hetero‐bimetallic Zn(II)2M(II) (M = Ca and Sr) complexes Zn2Ca(L)(OAc)2 (1) and Zn2Sr(L)(OAc)2 (2) with a novel asymmetrical bis(salamo)‐type tetraoxime ligand (H5L) were designed and ...synthesized, and characterized by elemental analyses, FT‐IR spectra, UV–vis absorption spectra, Density Functional Theory (DFT) calculation, Hirshfeld surface analyses and X‐ray single crystal diffractions. Compared with the symmetric bis(salamo)‐type ligands, the ligand H5L and its Zn(II)2M(II) (M = Ca and Sr) asymmetrical bis(salamo)‐type complexes synthesized for the first time in this paper have more novel structures and better properties. The results of ultraviolet titration show that the coordination ratio of ligand, alkaline earth metal and transition metal is 1:1:2. Complexes 1 and 2 have good luminescent properties and obvious antimicrobial activities.
Two hetero‐trinuclear Zn(II)2M(II) (M = Ca and Sr) bis(salamo)‐type complexes Zn2Ca(L)(OAc)2 (1) and Zn2Sr(L)(OAc)2 (2) were designed and synthesized, and characterized structurally. The coordination ratio and structure of the complexes were further determined by ultraviolet titration experiments. The results show that the coordination ratio of transition metal, alkaline earth metal and ligand is 2:1:1. The complexes have good properties, such as good luminescent properties and obvious antimicrobial activities.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune ...attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool ...specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a ...prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.
From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.
Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3-7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio HR, 10.98; 95%CI, 5.31-22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39-30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79-95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.
Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
