Adenosine triphosphate (ATP) is the most direct source of energy in organisms. This study is the first to demonstrate that ATP-aptamer complexes provide greater protection for unmodified gold ...nanoparticles (AuNPs) against salt-induced aggregation than either aptamer or ATP alone. This protective effect was confirmed using transmission electron microscopy, dynamic light scattering, Zeta potential measurement, and fluorescence polarization techniques. Utilizing controlled particle aggregation/dispersion as a gauge, a sensitive and selective aptasensor for colorimetric detection of ATP was developed using ATP-binding aptamers as the identification element and unmodified AuNPs as the probe. This aptasensor exhibited a good linear relationship between the absorbance and the logarithm concentration of ATP within a 50–1000nM range. ATP analogs such as guanosine triphosphate, uridine triphosphate and cytidine triphosphate resulted in little or no interference in the determination of ATP.
•The ATP-aptamer folding on the surface of unmodified AuNPs was first studied.•ATP-aptamer complexes could more effectively stabilize AuNPs than ATP or aptamer.•An ATP aptasensor was developed using label-free aptamers and unmodified AuNPs.•This aptasensor is highly sensitive and selective for ATP colorimetric detection.
Herein we described an efficient RhII‐catalyzed enantioselective cyclopropenation reaction of internal alkynes with a masked difluorodiazoethane reagent (PhSO2CF2CHN2, Ps‐DFA). This asymmetric ...transformation offers efficient access to a broad range of enantioenriched difluoromethylated cyclopropenes (40 examples, up to 99 % yield, 97 % ee). The synthetic utility of obtained strained carbocycles is demonstrated by subsequent stereodefined processes, including cross‐couplings, hydrogenation, Diels–Alder reaction, and Pauson–Khand reaction.
Three's a crowd: A highly enantioselective RhII‐catalyzed cyclopropenation reaction of difluorodiazoethane (PhSO2CF2CHN2) with challenging internal alkynes is reported (up to 99 % yield, 97 % ee). Versatile stereoselective transformations of these unique strained cyclopropenes are also demonstrated.
Background and Aim
Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose–effect relationship of keverprazan, ...a novel potassium‐competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole.
Methods
A randomized, double‐blind, double‐dummy, multicenter, low‐dose, high‐dose, and positive‐drug parallel‐controlled study was conducted to verify the non‐inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose–effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy.
Results
Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398).
Conclusions
Keverprazan was effective and non‐inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow‐up study of acid‐related disorders. (Trial registration number: ChiCTR2100043455.)
The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical ...hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF2H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron–chlorine (B–Cl) bond and the low-lying antibonding orbital of the carbon–chlorine (C–Cl) bond.
Supramolecular complexation is a powerful strategy for engineering materials in bulk and at interfaces. Metal–phenolic networks (MPNs), which are assembled through supramolecular complexes, have ...emerged as suitable candidates for surface and particle engineering owing to their diverse properties. Herein, we examine the supramolecular dynamics of MPNs during thermal transformation processes. Changes in the local supramolecular network including enlarged pores, ordered aromatic packing, and metal relocation arise from thermal treatment in air or an inert atmosphere, enabling the engineering of metal–oxide networks (MONs) and metal–carbon networks, respectively. Furthermore, by integrating photo‐responsive motifs (i.e., TiO2) and silanization, the MONs are endowed with reversible superhydrophobic (>150°) and superhydrophilic (≈0°) properties. By highlighting the thermodynamics of MPNs and their transformation into diverse materials, this work offers a versatile pathway for advanced materials engineering.
Supramolecular metal–phenolic networks, consisting of metal ions coordinated with phenolic motifs, can undergo selective thermodynamic transformations into nanoporous structures, including metal–carbon networks and metal–oxide networks, with tunable network organization and surface wettability.
A new nematode species of the genus Phasmarhabditis was isolated from the body surface of a slug (Philomycus bilineatus Benson, PB). Morphological and molecular analyses confirmed this nematode as a ...new species. The nematode was named Phasmarhabditis zhejiangensis sp. nov. (Nematoda: Rhabditidae) and is dioecious. In males, the open bursa with genital papillae is characterized by the formula 1-1-1-2-1-3, and the spicule length is 58μm. In female, the vulva is located approximately in the middle of the body. The nematode belongs to papillosa group because of its tail shape pointed with filiform tip. The phasmids are rod-shaped. The posterior anus is slightly swollen. P. zhejiangensis was further characterized by internal transcribed spacer (ITS), 18S rDNA and 28S rDNA sequences. After the sequencing results were compared with sequences available from the National Center for Biotechnology Information (NCBI), the maximum similarities of ITS, 18S and 28S sequences were 89.81%, 96.22% and 95.28%, respectively. Phylogenetic analyses placed Phasmarhabditis zhejiangensis sp. nov. in the genus Phasmarhabditis.
Functional coatings are of considerable interest because of their fundamental implications for interfacial assembly and promise for numerous applications. Universally adherent materials have recently ...emerged as versatile functional coatings; however, such coatings are generally limited to catechol, (ortho‐diphenol)‐containing molecules, as building blocks. Here, we report a facile, biofriendly enzyme‐mediated strategy for assembling a wide range of molecules (e.g., 14 representative molecules in this study) that do not natively have catechol moieties, including small molecules, peptides, and proteins, on various surfaces, while preserving the molecule's inherent function, such as catalysis (≈80 % retention of enzymatic activity for trypsin). Assembly is achieved by in situ conversion of monophenols into catechols via tyrosinase, where films form on surfaces via covalent and coordination cross‐linking. The resulting coatings are robust, functional (e.g., in protective coatings, biological imaging, and enzymatic catalysis), and versatile for diverse secondary surface‐confined reactions (e.g., biomineralization, metal ion chelation, and N‐hydroxysuccinimide conjugation).
The toolbox of metal–phenolic networks is expanded by enzyme‐mediated assembly, where a range of monophenols are converted into catechol‐containing molecules and cross‐linked by metal ions. This strategy preserves functionality of the monophenol precursors, while conferring benefits of catechol‐containing molecules (e.g., universal adhesion) to the networks.
Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID‐19) worldwide. We performed a meta‐analysis to investigate the efficacy and safety of bamlanivimab treatment in ...patients with COVID‐19. We searched articles from Web of Science, PubMed, Embase, the Cochrane Library, and medRxiv between January 30, 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID‐19. Our meta‐analysis retrieved three RCTs and seven cohort studies including 14 461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visits (RR 0.41, 95%CI 0.29−0.58), reduce ICU admission (RR 0.47, 95%CI 0.23−0.92), and mortality (RR 0.32, 95%CI 0.13−0.77) from the disease. The combination of bamlanivimab and etesevimab may have a greater potential for positive treatment outcomes. Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID‐19 to prevent hospitalization, reduce severity, and mortality from the disease. Combinations of bamlanivimab and etesevimab have a significant relative risk reduction for COVID‐related hospitalization or death for patients than the monotherapy 700 mg group. Well‐designed clinical trials to identify the clinical and biochemical characteristics in the COVID‐19 patients' population that could benefit from bamlanivimab or plus etesevimab are warranted in the future.
Highlights
Bamlanivimab could reduce the risk of hospitalization or emergency department (ED)visit.
Bamlanivimab could reduce the risk of mortality and ICU admission.
Combinations of bamlanivimab and etesevimab might have the better clinical efficacy.
Abstract
Background
The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related ...to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer.
Methods
We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR–Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research.
Results
We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology.
Conclusion
In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.
The manipulation of interfacial properties has broad implications for the development of high‐performance coatings. Metal–phenolic networks (MPNs) are an emerging class of responsive, adherent ...materials. Herein, host–guest chemistry is integrated with MPNs to modulate their surface chemistry and interfacial properties. Macrocyclic cyclodextrins (host) are conjugated to catechol or galloyl groups and subsequently used as components for the assembly of functional MPNs. The assembled cyclodextrin‐based MPNs are highly permeable (even to high molecular weight polymers: 250–500 kDa), yet they specifically and noncovalently interact with various functional guests (including small molecules, polymers, and carbon nanomaterials), allowing for modular and reversible control over interfacial properties. Specifically, by using either hydrophobic or hydrophilic guest molecules, the wettability of the MPNs can be readily tuned between superrepellency (>150°) and superwetting (ca. 0°).
Networking: The synthesis of host phenolic building blocks, consisting of macrocyclic host rings and phenolic coordinating functions, enables the rapid assembly of adherent conformal metal–phenolic network coatings on diverse substrates with modular and tunable interfacial properties using host–guest chemistry.
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