Rational synthesis of hydrogen‐bonded organic frameworks (HOFs) with predicted structure has been a long‐term challenge. Herein, by using the efficient, simple, low‐cost, and scalable ...mechanosynthesis, we demonstrate that reticular chemistry is applicable to HOF assemblies based on building blocks with different geometry, connectivity, and functionality. The obtained crystalline HOFs show uniform nano‐sized morphology, which is challenging or unachievable for conventional solution‐based methods. Furthermore, the one‐pot mechanosynthesis generated a series of Pd@HOF composites with noticeably different CO oxidation activities. In situ DRIFTS studies indicate that the most efficient composite, counterintuitively, shows the weakest CO affinity to Pd sites while the strongest CO affinity to HOF matrix, revealing the vital role of porous matrix to the catalytic performance. This work paves a new avenue for rational synthesis of HOF and HOF‐based composites for broad application potential.
Efficient and green mechanochemistry was performed to realize the reticular synthesis of hydrogen‐bonded organic frameworks with predictable structures. Moreover, a series of Pd@HOF composites were generated by the one‐pot mechanosynthesis, which showed different catalytic activities for CO oxidation. The synergetic effect between Pd and HOF was revealed by in situ DRIFTS, proving the application potential of functionalized HOF‐composites.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a ...diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Mammalian oocyte maturation depends on the translational activation of stored maternal mRNAs upon meiotic resumption. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a key oocyte ...factor that regulates maternal mRNA translation. However, the signal that triggers CPEB1 activation at the onset of mammalian oocyte maturation is not known. We provide evidence that a mitogen-activated protein kinase (MAPK) cascade couples maternal mRNA translation to meiotic cell cycle progression in mouse oocytes by triggering CPEB1 phosphorylation and degradation. Mutations of the phosphorylation sites or ubiquitin E3 ligase binding sites in CPEB1 have a dominant-negative effect in oocytes, and mimic the phenotype of ERK1/2 knockout, by impairing spindle assembly and mRNA translation. Overexpression of the CPEB1 downstream translation activator DAZL in ERK1/2-deficient oocytes partially rescued the meiotic defects, indicating that ERK1/2 is essential for spindle assembly, metaphase II arrest and maternal-zygotic transition (MZT) primarily by triggering the translation of key maternal mRNAs. Taken together, ERK1/2-mediated CPEB1 phosphorylation/degradation is a major mechanism of maternal mRNA translational activation, and is crucial for mouse oocyte maturation and MZT.
Embedding plasmonic metals in metal–organic frameworks (MOFs) can build an advanced visible‐light photocatalyst architecture utilizing the localized surface plasmon resonance (LSPR) effect, while the ...practical performances have been restricted by the sluggish charge transfer at metal–MOF interface and through the secondary building units (SBUs) of the adopted carboxylate MOFs currently. Herein, a pyrazolate Ni‐MOF (PFC‐9) featured with an 1D SBU chain is selected to be the host catalyst to immobilize Au nanoparticles as a novel and optimized construction for LSPR photocatalysis. Compared with the common 3D‐connected SBUs of carboxyl‐ZrOx and pyrazole‐NiOx configurations in the reference MOFs, the 1D (−Ni−NPz−NPz−)∞ chain in PFC‐9 creates abundant Au/MOF contacts, a short and low‐resistant pathway for Au‐to‐Ni2+ transport of hot electrons, and enables fluent electron utilization at the continuous active Ni sites. Consequently, the Au/PFC‐9 photocatalyst achieves the optimum activity for visible‐light‐driven H2 production. This work shows an example to promote the LSPR‐sensitized photocatalysis taking the advantage of MOFs’ structural tunability, providing significant guidance for the rational design of highly efficient photocatalysts.
A novel Au/MOF photocatalyst is constructed by taking the advantage of the pyrazole groups and catalytically active Ni2+ nodes in the 1D coordination chain of PFC‐9. The short‐range and low‐resistant hot‐electron transfer, from Au to Ni and throughout the continuous Ni sites, results in optimum activity for Au‐sensitized photocatalytic H2 production superior to cases without 1D pyrazolate secondary building units.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD
-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that ...SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.
Antibiotics are widely used in animals for disease treatment and prevention. After use, these antibiotics end up in manure. Here we investigated the fate of veterinary antibiotics in animal manure ...during composting and their residues in manure-applied soils. The results showed that 64.7% of the detected veterinary antibiotics were removed after composting for 171 days, which mainly occurred at the thermophilic phase in the second week, followed by a long stable stage with limited variations. The removal rates for lincomycin, trimethoprim and the macrolides during the composting were >89.7%, while those for the sulfonamides, tetracyclines and fluoroquinolones were less than <63.7%. The dissipation of antibiotics during the composting was related to the change of compost physicochemical properties, especially moisture and C/N ratio. The application of compost products with antibiotic residues could still lead to soil contamination, which may pose risks of resistance selection to the soil ecosystem.
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•17 veterinary antibiotics were detected during the 171 days of composting.•Tetracyclines and lincomycin were predominant in initial compost.•64.7% of detected antibiotics were removed during composting.•The removal of antibiotics mainly occurred in thermophilic phage.•Usage of compost product posed high risk of resistance selection in soil ecosystem.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Azomethine imines, as a prominent class of 1,3‐dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral ...azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper‐ or chiral phosphoric acid catalyzed ring‐closure reactions of N′‐(2‐alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy‐induced peripheral neuropathy (CIPN). Remarkably, the (S)‐ and (R)‐atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry.
The synthesis of axially chiral azomethine imines through copper‐ or chiral phosphoric acid (CPA)‐catalyzed ring closure of N′‐(2‐alkynylbenzylidene)hydrazides is described, showing high efficiency, mild conditions, broad scope, and excellent enantioselectivity. Biological studies revealed the neuroprotective activity of the S product for dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
The aim of this study was to evaluate the neuroprotective effects of SalB on high glucose (HG)‐induced excessive autophagy and apoptosis in vitro.
Methods
The proliferation and apoptosis ...of RSC96 cells were determined using the MTT assay and flow cytometry, respectively. Western blot analysis was performed to examine the expression of autophagy and apoptosis‐related proteins. RT‐PCR and flow cytometry were manipulated to examine the level of Bcl‐2. The signals of autophagy markers were detected using immunofluorescence methods.
Key findings
We found that HG significantly reduced RSC96 cell's proliferation and induced apoptosis. What's more, HG increased the level of autophagy and apoptosis‐related proteins. However, these effects were reversed by SalB. In addition, we also found that 3‐MA decreased the expression of LC3A/B and Beclin1, while the JNK inhibitor SP600125 reduced the levels of phosphorylated JNK, LC3A/B and Beclin1.
Conclusions
High glucose not only induced apoptosis but also caused autophagic cell death by activating the JNK pathway. These effects prevented by SalB in an opposite manner.
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A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide‐engineered self‐delivery ...nanomedicine (designated as ChiP‐CeR) for photodynamic‐triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP‐CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc‐K(Fmoc)‐PEG8‐CREKA. ChiP‐CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high‐mobility group box‐1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP‐CeR can also polarize M2‐type tumor‐associated macrophages (TAMs) into M1‐type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP‐CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.
A chimeric peptide‐engineered self‐delivery nanomedicine (designated as ChiP‐CeR) based on matrix tumor‐targeting peptide (designated as ChiP), photosensitizer (Ce6), and immune adjuvant (R837) is developed for photodynamic therapy and immunotherapy. ChiP‐CeR possess superior antitumor effects against primary and lung metastatic tumor, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as ...NP‐Mel) are fabricated to improve photodynamic performance by inhibiting PDT‐upregulated cyclooxygenase‐2 (COX‐2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic‐K(PpIX)CGNKRTR), which can encapsulate the COX‐2 inhibitor of meloxicam. The well dispersed NP‐Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP‐Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL‐6 and TNF‐α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP‐Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.
Tumor homing chimeric peptide rhomboids (designated as NP‐Mel) are developed to promote the targeting delivery of drugs to breast cancer overexpressing neuropilin receptors (NRPs). NP‐Mel decrease the secretion of prostaglandin E2 (PGE2) after photodynamic therapy (PDT), inducing the downregulation of pro‐inflammatory cytokines to reverse PDT induced inflammation for enhanced breast cancer treatment.
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